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How does the age of a parent affect the chances of occurrence of certain genetically transmitted diseases?

How does the age of a parent affect the chances of occurrence of certain genetically transmitted diseases?


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Do genetically transmitted age-related diseases (like hypertension, arthritis etc.)have the probability of occurring at an earlier(younger) age in the offspring if they are born at a later age to their parent(s)?


In some studies, they have observed either positive or negative association between maternal or paternal age (the age of mother or father at the time of delivery) and earlier development of genetically predisposed diseases, such as diabetes type 1 and certain cancers, in offspring.

Diabetes type 1

Maternal age and diabetes in childhood (BMJ, 2010):

… the risk of childhood onset diabetes [type 1] increases with maternal age: 5% for each five years of age… the main explanations are that biological programming of the child is in some way affected by the age of the mother, or perhaps the father…

Cancer

Parental age and risk of sporadic and familial cancer in offspring: implications for germ cell mutagenesis (Epidemiology, 1999)

We used the nationwide Swedish Family-Cancer Database to analyze the effect of parental age on cancer in offspring at ages 15-53 years… Maternal age was associated with sporadic melanoma and leukemia, causing a 30% excess if mothers were more than 40 years vs. less than 20 years of age. A marginal effect of about 10% of both maternal and paternal age was observed for sporadic breast cancer.

Paternal age increased the RR of sporadic nervous system cancer by about 15%. Accumulation of chromosomal aberrations and mutations during the maturation of germ cells may be a mechanism for these findings. In familial cancers of colon, melanoma, and thyroid, higher age showed an apparent protective effect, which was also noted for sporadic cervical cancer and melanoma.

Rheumatoid arthritis

Ages of onset suggestive of genetic anticipation in rheumatoid arthritis multicase sibships can be explained by observational bias (Rheumatology, 2007)

There was no significant correlation between the age of RA onset and the maternal or paternal ages of conception.

Cardiovascular disease

In one study, they have found no significant association between maternal age and blood pressure in children. There seem to be no studies about the effect of maternal/paternal age on early-onset heart disease.

On the other hand, offsprings are at increased risk of developing a cardiovascular disease early if their parents had it early (PLoS One, 2016).


In another study, they have observed that maternal ages <25 and >45 have been associated with increased frailty index: a sum of 8 conditions (cancer, lung disease, mental health problems, diabetes, heart disease, stroke, blood pressure and arthritis)

Maternal Age and Offspring Adult Health: Evidence From the Health and Retirement Study (Demography, 2012)

In summary, net of some obvious confounders, only maternal ages below 25 and above 45 are associated with negative offspring health outcomes. (see Fig 1 and Table 2)

The mechanisms thought to be responsible for the young maternal age-offspring health link are related to the physiological immaturity and sociodemographic disadvantage that often accompany young parenthood… On the other hand, the negative association between advanced maternal age and adult health is thought to be driven by the physiological reproductive aging of the mother.

In this study, they have not checked for the age of onset of diseases in offspring, though.


What does it mean to have a genetic predisposition to a disease?

A genetic predisposition (sometimes also called genetic susceptibility) is an increased likelihood of developing a particular disease based on a person's genetic makeup. A genetic predisposition results from specific genetic variations that are often inherited from a parent. These genetic changes contribute to the development of a disease but do not directly cause it. Some people with a predisposing genetic variation will never get the disease while others will, even within the same family.

Genetic variations can have large or small effects on the likelihood of developing a particular disease. For example, certain variants (also called mutations) in the BRCA1 or BRCA2 genes greatly increase a person's risk of developing breast cancer and ovarian cancer. Particular variations in other genes, such as BARD1 and BRIP1, also increase breast cancer risk, but the contribution of these genetic changes to a person's overall risk appears to be much smaller.

Current research is focused on identifying genetic changes that have a small effect on disease risk but are common in the general population. Although each of these variations only slightly increases a person's risk, having changes in several different genes may combine to increase disease risk significantly. Changes in many genes, each with a small effect, may underlie susceptibility to many common diseases, including cancer, obesity, diabetes, heart disease, and mental illness. Researchers are working to calculate an individual’s estimated risk for developing a common disease based on the combination of variants in many genes across their genome. This measure, known as the polygenic risk score, is expected to help guide healthcare decisions in the future.

In people with a genetic predisposition, the risk of disease can depend on multiple factors in addition to an identified genetic change. These include other genetic factors (sometimes called modifiers) as well as lifestyle and environmental factors. Diseases that are caused by a combination of factors are described as multifactorial. Although a person's genetic makeup cannot be altered, some lifestyle and environmental modifications (such as having more frequent disease screenings and maintaining a healthy weight) may be able to reduce disease risk in people with a genetic predisposition.


All About Genetics

What do you know about your family tree? Have any of your relatives had health problems that tend to run in families? Which of these problems affected your parents or grandparents? Which ones affect you or your brothers or sisters now? Which problems might you pass on to your children?

Thanks to advances in medical research, doctors now have the tools to understand much about how certain illnesses, or increased risks for certain illnesses, pass from generation to generation. Here are some basics about genetics.

Genes and Chromosomes

Each of us has a unique set of chemical blueprints affecting how our body looks and functions. These blueprints are contained in our DNA (deoxyribonucleic acid), long, spiral-shaped molecules found inside every cell. DNA carries the codes for genetic information and is made of linked pieces (or subunits) called nucleotides. Each nucleotide contains a phosphate molecule, a sugar molecule (deoxyribose), and one of four so-called "coding" molecules called bases (adenine, guanine, cytosine, or thymidine). The order (or sequence) of these four bases determines each genetic code.

The segments of DNA that contain the instructions for making specific body proteins are called genes. Scientists believe that human DNA carries about 25,000 protein-coding genes. Each gene may be thought of as a "recipe" you'd find in cookbook. Some are recipes for creating physical features, like brown eyes or curly hair. Others are recipes to tell the body how to produce important chemicals called enzymes (which help control the chemical reactions in the body).

Along the segments of our DNA, genes are neatly packaged within structures called chromosomes. Every human cell contains 46 chromosomes, arranged as 23 pairs (called autosomes), with one member of each pair inherited from each parent at the time of conception. After conception (when a sperm cell and an egg come together to make a baby), the chromosomes duplicate again and again to pass on the same genetic information to each new cell in the developing child. Twenty-two autosomes are the same in males and females. In addition, females have two X chromosomes and males have one X and one Y chromosome. The X and the Y are known as sex chromosomes.

Human chromosomes are large enough to be seen with a high-powered microscope, and the 23 pairs can be identified according to differences in their size, shape, and the way they pick up special laboratory dyes.

Genetic Problems

Errors in the genetic code or "gene recipe" can happen in a variety of ways. Sometimes information is missing from the code, other times codes have too much information, or have information that's in the wrong order.

These errors can be big (for example, if a recipe is missing many ingredients &mdash or all of them) or small (if just one ingredient is missing). But regardless of whether the error is big or small, the outcome can be significant and cause a person to have a disability or at risk of a shortened life span.

Abnormal Numbers of Chromosomes

When a mistake occurs as a cell is dividing, it can cause an error in the number of chromosomes a person has. The developing embryo then grows from cells that have either too many chromosomes or not enough.

In trisomy, for example, there are three copies of one particular chromosome instead of the normal two (one from each parent). Trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome) are examples of this type of genetic problem.

Trisomy 18 affects 1 out of every 7,500 births. Children with this syndrome have a low birth weight and a small head, mouth, and jaw. Their hands typically form clenched fists with fingers that overlap. They also might have birth defects involving the hips and feet, heart and kidney problems, and intellectual disability. Only about 5% of these children are expected to live longer than 1 year.

Trisomy 13 affects 1 out of every 15,000 to 25,000 births. Children with this condition often have cleft lip and palate, extra fingers or toes, foot abnormalities, and many different structural abnormalities of the skull and face. This condition also can cause birth defects of the ribs, heart, abdominal organs, and sex organs. Long-term survival is unlikely but possible.

In monosomy, another form of numerical error, one member of a chromosome pair is missing. So there are too few chromosomes rather than too many. A baby with a missing autosome has little chance of survival. However, a baby with a missing sex chromosome can survive in certain cases. For example, girls with Turner syndrome &mdash who are born with just one X chromosome &mdash can live normal, productive lives as long as they receive medical care for any health problems associated with their condition.

Deletions, Translocations, and Inversions

Sometimes it's not the number of chromosomes that's the problem, but that the chromosomes have something wrong with them, like an extra or missing part. When a part is missing, it's called a deletion (if it's visible under a microscope) and a microdeletion (if it's too tiny to be visible). Microdeletions are so small that they may involve only a few genes on a chromosome.

Some genetic disorders caused by deletions and microdeletions include Wolf-Hirschhorn syndrome (affects chromosome 4), Cri-du-chat syndrome (chromosome 5), DiGeorge syndrome (chromosome 22), and Williams syndrome (chromosome 7).

In translocations (which affect about 1 in every 400 newborns), bits of chromosomes shift from one chromosome to another. Most translocations are "balanced," which means there is no gain or loss of genetic material. But some are "unbalanced," which means there may be too much genetic material in some places and not enough in others. With inversions (which affect about 1 in every 100 newborns), small parts of the DNA code seem to be snipped out, flipped over, and reinserted. Translocations may be either inherited from a parent or happen spontaneously in a child's own chromosomes.

Both balanced translocations and inversions typically cause no malformations or developmental problems in the kids who have them. However, those with either translocations or inversions who wish to become parents may have an increased risk of miscarriage or chromosome abnormalities in their own children. Unbalanced translocations or inversions are associated with developmental and/or physical abnormalities.

Sex Chromosomes

Genetic problems also occur when abnormalities affect the sex chromosomes. Normally, a child will be a male if he inherits one X chromosome from his mother and one Y chromosome from his father. A child will be a female if she inherits a double dose of X (one from each parent) and no Y.

Sometimes, however, children are born with only one sex chromosome (usually a single X) or with an extra X or Y. Girls with Turner syndrome are born with only one X chromosome, whereas boys with Klinefelter syndrome are born with 1 or more extra X chromosomes ( XXY or XXXY).

Sometimes, too, a genetic problem is X-linked, meaning that it is associated with an abnormality carried on the X chromosome. Fragile X syndrome, which causes intellectual disability in boys, is one such disorder. Other diseases that are caused by abnormalities on the X chromosome include hemophilia and Duchenne muscular dystrophy.

Females may be carriers of these diseases, but because they also inherit a normal X chromosome, the effects of the gene change are minimized. Males, on the other hand, only have one X chromosome and are almost always the ones who show the full effects of the X-linked disorder.

Gene Mutations

Some genetic problems are caused by a single gene that is present but altered in some way. Such changes in genes are called mutations. When there is a mutation in a gene, the number and appearance of the chromosomes is usually still normal.

To pinpoint the defective gene, scientists use sophisticated DNA testing techniques. Genetic illnesses caused by a single problem gene include phenylketonuria (PKU), cystic fibrosis, sickle cell disease, Tay-Sachs disease, and achondroplasia (a type of dwarfism).

Although experts used to think that no more than 3% of all human diseases were caused by errors in a single gene, new research shows that this is an underestimate. Within the last few years, scientists have discovered genetic links to many different diseases that weren't originally thought of as genetic, including Parkinson's disease, Alzheimer's disease, heart disease, diabetes, and several different types of cancer. Alterations in these genes are thought to increase one's risk of developing these conditions.

Oncogenes (Cancer-Causing Genes)

Researchers have identified about 50 cancer-causing genes that greatly increase a person's odds of developing cancer. By using sophisticated tests, doctors may be able to identify who has these genetic mutations, and determine who is at risk.

For example, scientists have determined that colorectal cancer is sometimes associated with mutations in a gene called APC. They've also discovered that abnormalities in the BRCA1 and BRCA2 gene give women a 50% chance of developing breast cancer and an increased risk for ovarian tumors.

People who are known to have these gene mutations now can be carefully monitored by their doctors. If problems develop, they're more likely to get treated for cancer earlier than if they hadn't known of their risk, and this can increase their odds of survival.

New Discoveries, Better Care

Scientists have made major strides in the field of genetics over the last two decades. The mapping of the human genome and the discovery of many disease-causing genes has led to a better understanding of the human body. This has enabled doctors to provide better care to their patients and to increase the quality of life for people (and their families) living with genetic conditions.


Causes and Risk Factors

  • The extra chromosome 21 leads to the physical features and developmental challenges that can occur among people with Down syndrome. Researchers know that Down syndrome is caused by an extra chromosome, but no one knows for sure why Down syndrome occurs or how many different factors play a role.
  • One factor that increases the risk for having a baby with Down syndrome is the mother&rsquos age. Women who are 35 years or older when they become pregnant are more likely to have a pregnancy affected by Down syndrome than women who become pregnant at a younger age. 3-5 However, the majority of babies with Down syndrome are born to mothers less than 35 years old, because there are many more births among younger women. 6,7

Having a Baby After Age 35: How Aging Affects Fertility and Pregnancy

A woman&rsquos peak reproductive years are between the late teens and late 20s. By age 30, fertility (the ability to get pregnant) starts to decline. This decline becomes more rapid once you reach your mid-30s. By 45, fertility has declined so much that getting pregnant naturally is unlikely for most women.

Women begin life with a fixed number of eggs in their ovaries. The number of eggs decreases as women get older. Also, the remaining eggs in older women are more likely to have abnormal chromosomes. And as women age, they are at higher risk of disorders that can affect fertility, such as uterine fibroids and endometriosis.

For healthy couples in their 20s and early 30s, around 1 in 4 women will get pregnant in any single menstrual cycle. By age 40, around 1 in 10 women will get pregnant per menstrual cycle. A man&rsquos fertility also declines with age, but not as predictably.

Women who get pregnant later in life have a higher risk of complications. For example, pregnant women over 40 have an increased risk of preeclampsia. Pregnancy later in life also can affect the health of the fetus.

Older women tend to have more health problems than younger women. For example, high blood pressure is more common in older people. Having high blood pressure before pregnancy can increase the risk of preeclampsia. But studies also show that older women who do not have any health conditions can still have complicated pregnancies.

The overall risk of having a baby with a chromosome abnormality is small. But as a woman ages, the risk of having a baby with missing, damaged, or extra chromosomes increases.

Down syndrome (trisomy 21) is the most common chromosome problem that occurs with later childbearing. The risk of having a pregnancy affected by Down syndrome is

Learn about tests that look for genetic disorders:

Prenatal screening tests assess the risk that a pregnancy will be affected by a specific birth defect or genetic disorder. Screening can be done before and during pregnancy.

Prenatal diagnostic tests can detect if a pregnancy is affected by a specific birth defect or genetic disorder.

Both screening and diagnostic testing are offered to all pregnant women. You don&rsquot have to be a certain age or have a family history of a disorder to have these tests. It is your choice whether you want to have them done. Talk with your obstetrician&ndashgynecologist (ob-gyn) about genetic testing options so you can make a choice that&rsquos right for you.

The risks of miscarriage and stillbirth are greater in women who are older than 35. Also, multiple pregnancy is more common in older women than in younger women. As the ovaries age, they are more likely to release more than one egg each month.

Also, some fertility treatments increase the chance of a multiple pregnancy. Although multiple pregnancies can be healthy, these pregnancies can increase the risk of preterm birth.

All women should think about whether they would like to have children and, if so, when to have them. This is called a reproductive life plan. If you would like to have children someday, your plan can be a simple statement like, &ldquoI would like to finish school and have more money saved before having children&rdquo or &ldquoI would like to have children in my 20s when my chances for a healthy pregnancy are best.&rdquo Talking with your ob-gyn can help you develop your reproductive life plan. The next step is to put your plan into action.

If you don&rsquot want to get pregnant and have a male partner, use a birth control method to prevent pregnancy. Make sure you are using a method that fits your reproductive goals, your lifestyle, and any health conditions that you have. Together you and your ob-gyn can review your birth control options.

If you want to get pregnant soon, you should try to be as healthy as possible before pregnancy. Take steps to stop using alcohol, tobacco, and marijuana. You also should start taking a prenatal vitamin with folic acid to help prevent neural tube defects (NTDs).

This is a visit with your ob-gyn that helps you plan for a pregnancy. During this visit, your ob-gyn should review your medical history, your family history, any past pregnancies, and any medications you take. You also should review immunizations to be sure that you have all of the vaccines that are recommended for you. You and your ob-gyn also may talk about

how you can maintain a healthy weight before getting pregnant

the option of carrier screening for you and, if needed, your partner

All women should talk with their ob-gyns before trying to get pregnant, but it&rsquos especially important for women older than 35.

It is a good idea to talk about your plan once a year with your ob-gyn. Ask yourself whether you would like to have children in the next year. If your answer is yes, you can take steps for a healthy pregnancy. If your answer is no, you can make sure that you are using a reliable birth control method.

Currently, there is no medical technique that can guarantee fertility will be preserved. If you know that you want to have children later in life, one option may be in vitro fertilization (IVF). With IVF, sperm is combined with a woman&rsquos eggs in a laboratory. If the sperm fertilizes the eggs, embryos may grow.

Embryos can be frozen and used many years later. When you are ready, an embryo can be transferred to your uterus to try to achieve a pregnancy. The chance that IVF will work for you depends on many factors, including your health and your age when the embryos are frozen.

Talking with a fertility expert will help you understand your chances of success with IVF. Also, there are financial considerations. Some IVF treatments are expensive and may not be covered by insurance.

A procedure called oocyte cryopreservation&mdash&ldquofreezing your eggs&rdquo&mdashhas become more popular in recent years. In this procedure, several eggs are removed from the ovaries. The unfertilized eggs are then frozen for later use in IVF.

Egg freezing may seem like a good option for women who want to delay childbearing. But egg freezing is recommended mainly for women having cancer treatment that will affect their future fertility. There is not enough research to recommend routine egg freezing for the sole purpose of putting off childbearing. Egg freezing also is expensive and may not be covered by insurance.

If you are older than 35 and have not gotten pregnant after 6 months of having regular sex without using birth control, talk with your ob-gyn about an infertility evaluation. If you are older than 40, an evaluation is recommended before you try to get pregnant. This advice is especially true if you have a problem that could affect fertility, such as endometriosis.

During an evaluation, you have physical exams and tests to try to find the cause of infertility. If a cause is found, treatment may be possible. In many cases, infertility can be successfully treated even if no cause is found. But the chances of success with these treatments decline with age. See Evaluating Infertility for more information.

Getting early and regular prenatal care may increase your chances of having a healthy baby. At each visit, your health and your fetus&rsquos health should be monitored. If you have a preexisting medical condition or if a medical condition develops during pregnancy, you may need to see your ob-gyn more often. Regular prenatal care can help your ob-gyn find problems sooner and take steps to help manage them.

Carrier Screening: A test done on a person without signs or symptoms to find out whether he or she carries a gene for a genetic disorder.

Chromosomes: Structures that are located inside each cell in the body. They contain the genes that determine a person&rsquos physical makeup.

Complications: Diseases or conditions that happen as a result of another disease or condition. An example is pneumonia that occurs as a result of the flu. A complication also can occur as a result of a condition, such as pregnancy. An example of a pregnancy complication is preterm labor.

Diagnostic Tests: Tests that look for a disease or cause of a disease.

Down Syndrome (Trisomy 21): A genetic disorder that causes abnormal features of the face and body, medical problems such as heart defects, and mental disability. Most cases of Down syndrome are caused by an extra chromosome 21 (trisomy 21).

Eggs: The female reproductive cells made in and released from the ovaries. Also called the ova.

Embryos: The stage of prenatal development that starts at fertilization (joining of an egg and sperm) and lasts up to 8 weeks.

Endometriosis: A condition in which tissue that lines the uterus is found outside of the uterus, usually on the ovaries, fallopian tubes, and other pelvic structures.

Fetus: The stage of human development beyond 8 completed weeks after fertilization.

Fibroids: Growths that form in the muscle of the uterus. Fibroids usually are noncancerous.

Folic Acid: A vitamin that reduces the risk of certain birth defects when taken before and during pregnancy.

Genetic Disorders: Disorders caused by a change in genes or chromosomes.

High Blood Pressure: Blood pressure above the normal level. Also called hypertension.

In Vitro Fertilization (IVF): A procedure in which an egg is removed from a woman&rsquos ovary, fertilized in a laboratory with the man&rsquos sperm, and then transferred to the woman&rsquos uterus to achieve a pregnancy.

Menstrual Cycle: The monthly process of changes that occur to prepare a woman&rsquos body for possible pregnancy. A menstrual cycle is defined as the first day of menstrual bleeding of one cycle to the first day of menstrual bleeding of the next cycle.

Miscarriage: Loss of a pregnancy that is in the uterus.

Multiple Pregnancy: A pregnancy where there are two or more fetuses.

Neural Tube Defects (NTDs): Birth defects that result from a problem in development of the brain, spinal cord, or their coverings.

Obstetrician&ndashGynecologist (Ob-Gyn): A doctor with special training and education in women&rsquos health.

Oocyte Cryopreservation: A procedure in which eggs are removed from a woman&rsquos ovaries and frozen for later use with in vitro fertilization (IVF).

Ovaries: Organs in women that contain the eggs necessary to get pregnant and make important hormones, such as estrogen, progesterone, and testosterone.

Preeclampsia: A disorder that can occur during pregnancy or after childbirth in which there is high blood pressure and other signs of organ injury. These signs include an abnormal amount of protein in the urine, a low number of platelets, abnormal kidney or liver function, pain over the upper abdomen, fluid in the lungs, or a severe headache or changes in vision.

Prenatal Care: A program of care for a pregnant woman before the birth of her baby.

Preterm: Less than 37 weeks of pregnancy.

Screening Tests: Tests that look for possible signs of disease in people who do not have signs or symptoms.

Sexually Transmitted Infections (STIs): Infections that are spread by sexual contact. Infections include chlamydia, gonorrhea, human papillomavirus (HPV), herpes, syphilis, and human immunodeficiency virus (HIV, the cause of acquired immunodeficiency syndrome [AIDS]).

Sperm: A cell made in the male testicles that can fertilize a female egg.

Stillbirth: Birth of a dead fetus.

Uterus: A muscular organ in the female pelvis. During pregnancy, this organ holds and nourishes the fetus. Also called the womb.

Vaccines: Substances that help the body fight disease. Vaccines are made from very small amounts of weak or dead agents that cause disease (bacteria, toxins, and viruses).


Overview of Huntington’s Disease

HD affects the whole brain, but certain areas are more vulnerable than others. Pictured above in blue is the striatum – an area deep in the brain that plays a key role in movement, mood, and behavior control. The striatum is the part of the brain that is most affected by HD.

What Is Huntington’s Disease?

Huntington’s disease (HD) is a brain disease that is passed down in families from generation to generation. It is caused by a mistake in the DNA instructions that build our bodies and keep them running. DNA is made up of thousands of genes, and people with HD have a small error in one gene, called huntingtin. Over time this error causes damage to the brain and leads to HD symptoms.

HD causes deterioration in a person’s physical, mental, and emotional abilities, usually during their prime working years, and currently has no cure. Most people start developing symptoms during adulthood, between the ages of 30 to 50, but HD can also occur in children and young adults (known as juvenile HD or JHD). HD is known as a family disease because every child of a parent with HD has a 50/50 chance of inheriting the faulty gene. Today, there are approximately 41,000 symptomatic Americans and more than 200,000 at-risk of inheriting the disease.

Symptoms of Huntington’s Disease

The symptoms of HD can vary a lot from person to person, but they usually include:

  • Personality changes, mood swings & depression
  • Forgetfulness & impaired judgment
  • Unsteady gait & involuntary movements (chorea)
  • Slurred speech, difficulty in swallowing & significant weight loss

Most people with HD experience problems with thinking, behavior, and movements. Symptoms usually worsen over the course of 10 to 25 years and affect the ability to reason, walk, and talk. Early on, a person with HD or their friends and family may notice difficulties with planning, remembering, and staying on task. They may develop mood changes like depression, anxiety, irritability, and anger. Most people with HD become “fidgety” and develop movements of the face and limbs known as chorea, which they are not able to control.

Because of the uncontrolled movements (chorea), a person with HD may lose a lot of weight without intending to, and may have trouble walking, balancing, and moving around safely. They will eventually lose the ability to work, drive, and manage tasks at home, and may qualify for disability benefits. Over time, the individual will develop difficulty with speaking and swallowing, and their movements will become slow and stiff. People with advanced HD need full-time care to help with their day-to-day activities, and they ultimately succumb to pneumonia, heart failure or other complications. The symptoms of HD are sometimes described as having ALS, Parkinson’s and Alzheimer’s – simultaneously.

The Huntingtin Gene & Protein

The DNA error that causes HD is found in a gene called huntingtin. This gene was discovered in 1993. Everyone has the huntingtin gene, but only those that inherit the mistake, known as the HD mutation, will develop HD and risk passing it on to their children. Genes are made up of the nucleotide “letters” A,G,C, and T, which form a code that is read in groups of three. HD is caused by a stretch of the letters C-A-G in the huntingtin gene which repeat over and over, too many times…CAGCAGCAGCAGCAG. This is known as a CAG repeat expansion. In the huntingtin gene, most people have around 20 CAG repeats, but people with HD have around 40 or more. Every person who has this CAG repeat expansion in the HD gene will eventually develop the disease, and each of their children has a 50% chance of developing HD.

Our genes are like an instruction manual for making proteins, the machines that run everything in our bodies. The huntingtin gene (DNA) contains instructions that are copied into a biological message (RNA) which makes the huntingtin protein. The huntingtin protein is very large and seems to have many functions, especially as the brain is developing before birth, but it is not fully understood. We know that the extra CAG repeats in people with HD cause the huntingtin protein to be extra-long and difficult to maintain, which makes it difficult for it to do its job. Over many years, this “mutant” huntingtin protein forms clumps in brain cells, and causes them to become damaged and die. The most vulnerable part of the brain in HD is called the striatum, and it controls movement, mood, and memory. Damage to the striatum over time is what causes the symptoms of HD.

Treating Huntington’s Disease

There is currently no cure or treatment which can halt, slow or reverse the progression of the disease. However, there are many treatments and interventions that can help to manage HD symptoms. A neurologist, psychiatrist, or nurse with expertise in HD may prescribe medications to ease anxiety and depression, help with troublesome

behaviors, and calm uncontrolled movements. A psychologist or social worker can provide individual or group counseling. Physical and occupational therapists can work with patients and families to develop strength, move safely, and adjust the home environment and activities as needed. Speech language pathologists and nutritionists can help with communication, eating and swallowing safely, and combating weight loss. Clinician researchers may suggest participation in HD clinical trials.

Social and community support is an important part of HD care. Family, friends, loved ones, and companions often assume many of the HD person’s former responsibilities and help with daily activities and care routines when they can no longer do so themselves. Caregivers and kids may also need support for the challenges and stresses that come with HD.


Impact of Tourette syndrome

Having TS can have an impact on many areas of life, particularly when children have another condition in addition to TS. Using data from CDC studies, the following are examples of the impact of TS.

Education

Compared to children without TS, children with TS were more likely to 5

  • Have an individualized education program (IEP)
  • Have a parent contacted about school problems and
  • Not complete their homework.

Once the presence of other disorders was taken into account, children with TS were still more likely to have an IEP compared to children without TS.

Health and healthcare

Compared to children without TS, children with TS were more likely to have 6

  • A chronic health condition
  • A special healthcare need
  • Received mental health treatment and
  • Needs for mental health care that were not met.

Compared to children without TS, children with TS were less likely to have

Parenting

Compared to children without TS, children with TS were more likely to have parents with high levels of stress and frustration. 7

Once the presence of other disorders was taken into account, parents of children with Tourette were still more likely to have high levels of stress and frustration.

Social competence

Compared to children without TS, children with TS were more likely to struggle with 8

  • Social competence
  • Higher levels of behavioral problems and
  • Lower levels of social skills.

This is particularly true when children have moderate-to-severe TS and when they are diagnosed with other mental, emotional, or behavioral disorders.

Bullying involvement

Compared to children without TS, children with TS were 2

  • More likely to be the victim of bullying
  • More likely to be the perpetrator of bullying and
  • More likely to be both a victim and a perpetrator.

Bullying is most common among peers, but children with TS also experience being treated differently by teachers and other adults. 9


Genetic causality in mental disorders

As of 2002, genes appear to influence the development of mental disorders in three major ways: they may govern the organic causes of such disorders as Alzheimer's disease and schizophrenia they may be responsible for abnormalities in a person's development before or after birth and they may influence a person's susceptibility to anxiety, depression, personality disorders , and substance abuse disorders.

One technological development that has contributed to the major advances in biological psychiatry in the last twenty years is high-speed computing. Faster computers have enabled researchers to go beyond rough estimates of the heritability of various disorders to accurate quantification of genetic effects. In some cases the data have led to significant reappraisals of the causes of specific disorders. As recently as the 1960s and 1970s, for example, schizophrenia was generally attributed to "refrigerator mothers" and a chilly emotional climate in the patients' extended families. As of 2002, however, the application of computer models to schizophrenia indicates that the heritability of the disorder may be as high as 80%. Another instance is autism , which was also blamed at one time on faulty parenting but is now known to be 90+% heritable.

Mental disorders with organic causes

The two most important examples of mental disorders caused by organic changes or abnormalities in the brain are late-onset Alzheimer's disease and schizophrenia. Both disorders are polygenic , which means that their expression is determined by more than one gene. Another disorder that is much less common, Huntington's disease, is significant because it is one of the few mental disorders that is monogenic , or determined by a single gene.

SCHIZOPHRENIA. Researchers have known for many years that first-degree biological relatives of patients with schizophrenia have a 10% risk of developing the disorder, as compared with 1% in the general population. The identical twin of a person with schizophrenia has a 40%&ndash50% risk. The first instance of a specific genetic linkage for schizophrenia, however, was discovered in 1987 by a group of Canadian researchers at the University of British Columbia. A case study that involved a Chinese immigrant and his 20-year-old nephew, both diagnosed with schizophrenia, led the researchers to a locus on the short arm of chromosome 5. In 1988, a study of schizophrenia in several Icelandic and British families also pointed to chromosome 5. Over the course of the next decade, other studies of families with a history of schizophrenia indicated the existence of genes related to the disorder on other chromosomes. In late 2001, a multidisciplinary team of researchers reported positive associations for schizophrenia on chromosomes 15 and 13. Chromosome 15 is linked to schizophrenia in European American families as well as some Taiwanese and Portuguese families. A recent study of the biological pedigrees found among the inhabitants of Palau (an isolated territory in Micronesia) points to chromosomes 2 and 13. Still another team of researchers has suggested that a disorder known as 22q deletion syndrome may actually represent a subtype of schizophrenia, insofar as people with this syndrome have a 25% risk of developing schizophrenia.

ALZHEIMER'S DISEASE. Late-onset Alzheimer's disease (AD) is unquestionably a polygenic disorder. It has been known since 1993 that a specific form of a gene for apolipoprotein E (apoE4) on human chromosome 19 is a genetic risk factor for late-onset Alzheimer's. People who have the apoE4 gene from one parent have a 50% chance of developing AD a 90% chance if they inherited the gene from both parents. They are also likely to develop AD earlier in life. One of the remaining puzzles about this particular gene, however, is that it is not a consistent marker for AD. In other words, some people who have the apoE4 gene do not develop Alzheimer's, and some who do not have the gene do develop the disorder. In 1998, another gene on chromosome 12 that controls the production of bleomycin hydrolase (BH) was identified as a second genetic risk factor that acts independently of the apoE gene. In December 2000, three separate research studies reported that a gene on chromosome 10 that may affect the processing of amyloid-beta protein is also involved in the development of late-onset AD.

There are two other forms of AD, early-onset AD and familial Alzheimer's disease (FAD), which have different patterns of genetic transmission. Early-onset AD is caused by a defect in one of three genes known as APP, presenilin-1, and presenilin-2, found on human chromosomes 21, 14, and 1, respectively. Early-onset AD is also associated with Down syndrome, in that persons with trisomy 21 (three forms of human chromosome 21 instead of a pair) often develop this form of Alzheimer's. The brains of people with Down syndrome age prematurely, so that those who develop early-onset AD are often only in their late 40s or early 50s when the symptoms of the disease first appear. Familial Alzheimer's disease appears to be related to abnormal genes on human chromosomes 21 and 14.

HUNTINGTON'S DISEASE. Huntington's disease, or Huntington's chorea, is a neurological disorder that kills the cells in the caudate nucleus, the part of the brain that coordinates movement. It also destroys the brain cells that control cognitive functions. In 1983, the gene that causes Huntington's disease was discovered on the short arm of human chromosome 4. Ten years later, the gene was identified as an instance of a triplet or trinucleotide repeat. Nucleotides are the molecular "building blocks" of DNA and RNA. Three consecutive nucleotides form a codon, or triplet, in messenger RNA that codes for a specific amino acid. In 1991, researchers discovered not only that nucleotide triplets repeat themselves, but that these repetitions sometimes expand in number during the process of genetic transmission. This newly discovered type of mutation is known as a dynamic or expansion mutation. Since 1991, more than a dozen diseases have been traced to expansion mutations. Eight of them are caused by repeats of the triplet cytosine-adenine-guanine (CAG), which codes for an amino acid called glutamine. In 1993, Huntington's disease was identified as a CAG expansion mutation disorder. Where the genetic material from a normal chromosome 4 has about 20 repeats of the CAG triplet, the Huntington's gene has a minimum of 45 repeats, sometimes as many as 86. The higher the number of CAG triplet repeats in a Huntington's gene, the earlier the age at which the symptoms will appear. The expansion mutation in Huntington's disease results in the production of a toxic protein that destroys the cells in the patient's brain that control movement and cognition.

Childhood developmental disorders

Developmental disorders of childhood are another large category of mental disorders caused by mutations, deletions, translocations (rearrangements of the arms of chromosomes) and other alterations in genes or chromosomes.

TRIPLET REPEAT DISORDERS. Since 1991, expansion mutations have been identified as the cause of thirteen different diseases. Some, like Huntington's disease, are characterized by long expansion mutations of the trinucleotide sequence CAG, which in effect adds so much glutamine to the protein being synthesized that it becomes toxic to the nervous system. A second category of triplet repeat disorders contains extra triplets that add an amino acid called alanine to the protein. The sequence of nucleotides is cytosine-guanine-N, where N stands for any of the four basic nucleotides. Although the proteins produced by this type of expansion mutation are not toxic, their normal function in the body is disrupted. The developmental disorders related to these CGN triplets are characterized by abnormalities of the skeleton. One of these disorders is synpolydactyly, in which the patient has more than the normal number of fingers or toes. Another is cleidocranial dysplasia, a disorder marked by abnormal development of the skull.

Other developmental disorders are caused by expansion mutations outside the regions of the gene that code for proteins. The segments of DNA that specify the sequence of a portion of a protein are known as exons , while the stretches of DNA that lie between the exons and do not code for proteins are called introns . The CAG and CGN groups of triplet disorders described in the preceding paragraph are expansion mutations that occur within exons. A third group of triplet disorders results from expansion mutations in introns. Expansions in this third group are usually much longer than those in the first two categories some repeat several hundred or even several thousand times. The best-known expansion mutation in this group causes the disorder known as fragile X syndrome. Fragile X syndrome is the most common inherited form of mental retardation and should be considered in the differential diagnosis of any child with developmental delays, mental retardation, or learning difficulties. The syndrome is caused by a large expansion of a cytosine-guanine-guanine (CGG) repeat which interferes with normal protein transcription from a gene called the FMR1 gene on the X chromosome. Males with the mutation lack a second normal copy of the gene and are more severely affected than females who have a normal FMR1 gene on their second X chromosome. In both sexes there is a correlation between the length of the expansion mutation and the severity of the syndrome.

The discovery of expansion mutations was the solution to a long-standing genetic riddle. Clinicians had noticed as early as 1910 that some disorders produce a more severe phenotype or occur at earlier and earlier ages in each successive generation of an affected family. This phenomenon is known as anticipation , but its biological basis was not understood until recently. It is now known that triplet repeats that are long enough to cause disorders are unstable and tend to grow longer from generation to generation. For example, an expansion mutation of the cytosine-thymine-guanine (CTG) triplet causes a potentially life-threatening developmental disorder known as myotonic dystrophy. Repeats of the CTG triplet that are just above the threshold for myotonic dystrophy itself may produce a relatively mild disorder, namely eye cataracts in later life. Within two to three generations, however, the CTG repeats become longer, producing a fatal congenital illness. In addition to developmental disorders of childhood, expansion mutations may also be involved in other psychiatric disorders. Anticipation has been found in some families affected by bipolar disorder and schizophrenia, and some researchers think that it may also be present in some forms of autism.

GENOMIC IMPRINTING. Another recent discovery in the field of biological psychiatry is the phenomenon of genomic imprinting, which distinguishes between chromosomes derived from a person's father and those derived from the mother. Genomic imprinting was discovered in the late 1980s as an exception to Gregor Mendel's laws of biological inheritance. A small subset of human genes are expressed differently depending on the parent who contributes them to a child's genetic makeup. This phenomenon has helped researchers understand the causation of three well-known genetic disorders&mdash Prader-Willi, Angelman, and Beckwith-Wiedemann syndromes.

In the 1980s, researchers studying Prader-Willi syndrome and Angelman syndrome noticed that both disorders were caused by a deletion on the long arm of chromosome 15 in the very same region, extending from 15q11 to 15q13. This finding was surprising, because the two syndromes have markedly different phenotypes. Children with Prader-Willi syndrome have severe mental retardation, poor muscle tone, small hands and feet, and a voracious appetite (hyperphagia) that begins in childhood. As a result, they are often obese by adolescence. Children with Angelman syndrome, on the other hand, do not speak, are often hyperactive, and suffer from seizures and sleep disturbances. In the late 1980s, advances in molecular genetics revealed that the different expressions of the same deletion on the same chromosome were determined by the sex of the parent who contributed that chromosome. Children with Prader-Willi syndrome had inherited their father's copy of chromosome 15 while the children with Angelman syndrome had inherited their mother's. Highly specific diagnostic tests for these two disorders have been developed within the past decade.

Beckwith-Wiedemann syndrome is an overgrowth condition in which patients develop abnormally large bodies. They often have low blood sugar at birth and are at high risk for developing Wilms tumor, a childhood form of kidney cancer. Beckwith-Wiedemann syndrome is caused by several different genetic mutations that affect imprinted genes on chromosome 11p15. One of these imprinted genes governs the production of a growth factor that is responsible for the children's large body size.

BEHAVIORAL PHENOTYPES. Although medical professionals are familiar with the physical phenotypes associated with genetic disorders, the notion of behavioral phenotypes is still controversial. A behavioral phenotype is the characteristic set of behaviors found in patients with a genetic disorder. Behavioral phenotypes include patterns of language usage, cognitive development, and social adjustment as well as behavioral problems in the narrow sense. It is important for psychiatrists who treat children and adolescents to understand behavioral phenotypes, because they are better able to identify problem behaviors as part of a genetic syndrome and refer children to a geneticist for an accurate genetic diagnosis.

Examples of behavioral phenotypes are those associated with Down, Prader-Willi, and Williams syndromes. Children with Down syndrome have an increased risk of developing early-onset Alzheimer's disease. They are usually quiet and good-tempered, but may also be hyperactive and impulsive. Their behavioral phenotype includes delayed language development and moderate to severe mental retardation.

Children with Prader-Willi syndrome are often quiet in childhood but develop stubborn, aggressive, or impulsive patterns of behavior as they grow older. The onset of their hyperphagia is often associated with temper tantrums and other behavioral problems. They are typically obsessed with food, frequently hoarding it, stealing it, or stealing money to buy food. About 50% of children diagnosed with Prader-Willi syndrome meet the criteria for obsessive-compulsive disorder (OCD).

Williams syndrome is a genetic disorder that results from a deletion of locus 23 on chromosome 7q11. Children with this syndrome often have an "elf-like" face with short upturned noses and small chins. Their behavioral phenotype includes talkativeness, friendliness, and a willingness to follow strangers. They are also hyperactive and easily distracted from tasks. The personality profile of children with Williams syndrome is so distinctive that many are diagnosed on the basis of the behavioral rather than the physical phenotype.

Psychological/behavioral vulnerability in adults

Although psychiatrists at one time regarded emotional wounds in early childhood as the root cause of anxiety and depressive disorders in later life, inherited vulnerability to these disturbances is the subject of intensive study at the present time. In the past two decades, genetic factors have been shown to influence the likelihood of a person's developing mood disorders or post-traumatic syndromes in adult life. A study done in 1990 showed that first-degree relatives of a person diagnosed with major depression were two to four times as likely to develop depression themselves as people in the general population. As of 2002, however, the genetic patterns involved in depression appear to be quite complex there is some evidence that both genomic imprinting and the phenomenon of anticipation may be present in some families with multigenerational histories of depression. In addition, the evidence indicates that susceptibility to major depression is governed by several different genes on several different chromosomes. At present, genetic factors are thought to account for about 40% of a person's risk of depression, with environmental factors and personal temperament accounting for the remaining 60%.

With regard to manic depression, twin studies have shown that the twin of a patient diagnosed with manic depression has a 70%&ndash80% chance of developing the disorder. As of January 2002, a team of German researchers studying 75 families with a total of 275 members diagnosed with manic depression (out of 445 persons) has narrowed its search for genes for manic depression to one locus on human chromosome 10 and another on the long arm of chromosome 8.

POST-TRAUMATIC SYNDROMES. Researchers have found that some persons are more vulnerable than others to developing dissociative and anxiety-related symptoms following a traumatic experience. Vulnerability to trauma is affected by such inherited factors as temperament as well as by family or cultural influences shy or introverted persons are at greater risk for developing post-traumatic stress disorder (PTSD) than their extroverted or outgoing peers. In addition, twin studies indicate that certain abnormalities in brain hormone levels and brain structure are inherited, and that these increase a person's susceptibility to developing acute stress disorder (ASD) or PTSD following exposure to trauma.

ANXIETY DISORDERS. It has been known for some time that anxiety disorders tend to run in families. Recent twin studies as well as the ongoing mapping of the human genome point to a genetic factor in the development of generalized anxiety disorder (GAD). One study determined the heritability of GAD to be 0.32.

Recent research has also confirmed earlier hypotheses that there is a genetic component to agoraphobia , and that it can be separated from susceptibility to panic disorder (PD). In 2001 a team of Yale geneticists reported the discovery of a genetic locus on human chromosome 3 that governs a person's risk of developing agoraphobia. Panic disorder was found to be associated with two loci, one on human chromosome 1 and the other on chromosome 11q. The researchers concluded that agoraphobia and PD are common, heritable anxiety disorders that share some but not all of their genetic loci for susceptibility.

BEHAVIORAL TRAITS. There has been considerable controversy in the past decade concerning the mapping of genetic loci associated with specific human behaviors, as distinct from behavioral phenotypes related to developmental disorders. In 1993 a group of Dutch researchers at a university-affiliated hospital in Nijmegen reported that a mutation in a gene that governs production of a specific enzyme (monoamine oxidase A or MAOA) appeared to be the cause of violent antisocial behavior in several generations of males in a large Dutch family. At least fourteen men from this family had been in trouble with the law for unprovoked outbursts of aggression, ranging from arson and attacks on employers to sexual assaults on female relatives. Tests of the men's urine indicated that neurotransmitters secreted when the body responds to stress were not being cleared from the bloodstream, which is the normal function of MAOA. In other words, the genetic mutation resulted in an overload of stress-related neurotransmitters in the men's bodies, which may have primed them to act out aggressively. As of 2002, however, the Dutch findings have not been replicated by other researchers.

Another controversial study in the early 1990s concerned the possible existence of "gay genes" as a factor in human homosexuality. A researcher at the Salk Institute found that cells in the hypothalamus, a structure in the brain associated with the regulation of temperature and sleep cycles, were over twice as large in heterosexual males as in homosexual men. Although the researcher acknowledged that the structural differences may have arisen in adult life and were not necessarily present at birth, he raised the possibility that sexual orientation may have a genetic component. Another study of affected sibling pairs reported a possible locus for a "gay gene" on the X chromosome, but as of 2002 the results have not been replicated elsewhere.

In general, however, research into the genetic component of human behavior is presently conducted with one eye, so to speak, on the social and political implications of its potential results. Given contemporary concerns about the misuse of findings related to biological race or sex, investigators are usually careful to acknowledge the importance of environmental as well as genetic factors.


Type 1 Diabetes Risk Factors

There are several risk factors that may make it more likely that you’ll develop type 1 diabetes—if you have the genetic marker that makes you susceptible to diabetes. That genetic marker is located on chromosome 6, and it’s an HLA (human leukocyte antigen) complex. Several HLA complexes have been connected to type 1 diabetes, and if you have one or more of those, you may develop type 1. (However, having the necessary HLA complex is not a guarantee that you will develop diabetes in fact, less than 10% of people with the “right” complex(es) actually develop type 1.)

Other risk factors for type 1 diabetes include:

Viral infections: Researchers have found that certain viruses may trigger the development of type 1 diabetes by causing the immune system to turn against the body—instead of helping it fight infection and sickness. Viruses that are believed to trigger type 1 include: German measles, coxsackie, and mumps.

Race/ethnicity: Certain ethnicities have a higher rate of type 1 diabetes. In the United States, Caucasians seem to be more susceptible to type 1 than African-Americans and Hispanic-Americans. Chinese people have a lower risk of developing type 1, as do people in South America.

Geography: It seems that people who live in northern climates are at a higher risk for developing type 1 diabetes. It’s been suggested that people who live in northern countries are indoors more (especially in the winter), and that means that they’re in closer proximity to each other—potentially leading to more viral infections.

Conversely, people who live in southern climates—such as South America—are less likely to develop type 1. And along the same lines, researchers have noticed that more cases are diagnosed in the winter in northern countries the diagnosis rate goes down in the summer.

Family history: Since type 1 diabetes involves an inherited susceptibility to developing the disease, if a family member has (or had) type 1, you are at a higher risk.

If both parents have (or had) type 1, the likelihood of their child developing type 1 is higher than if just one parent has (or had) diabetes. Researchers have noticed that if the father has type 1, the risk of a child developing it as well is slightly higher than if the mother or sibling has type 1 diabetes.

Early diet: Researchers have suggested a slightly higher rate of type 1 diabetes in children who were given cow’s milk at a very young age.

Other autoimmune conditions: As explained above, type 1 diabetes is an autoimmune condition because it causes the body’s immune system to turn against itself. There are other autoimmune conditions that may share a similar HLA complex, and therefore, having one of those disorders may make you more likely to develop type 1.

Other autoimmune conditions that may increase your risk for type 1 include: Graves' disease, multiple sclerosis, and pernicious anemia.


What diseases or injuries can cause color blindness?

Color blindness can also happen if your eyes or the part of your brain that helps you see color gets damaged. This can be caused by:

  • Eye diseases, like glaucoma or macular degeneration
  • Brain and nervous system diseases, like Alzheimer’s or multiple sclerosis
  • Some medicines, like Plaquenil (a rheumatoid arthritis medicine)
  • Eye or brain injuries

Your color vision may also get worse as you get older, especially if you get a cataract — a cloudy area on your eye.