Human Genetic Disorders

Autosomal Recessive Disorders Requires the inheritance of two recessive alleles Error found on chromosomes 1 - 22

Albinism Inability to make melanin which gives pigmentation to hair, eyes, and skin Mutation in the tyrosinase gene on chromosome #11 Tyrosinase is an enzyme that functions in the production of melanin

Problems Visual Problems that cannot be corrected with glasses Sunburn VERY easily Life expectancy is normal http://albinism.med.umn.edu/facts.htm Incidence is 1 in 17,000 births. 18,000 cases in USA

Cystic Fibrosis Results in thick, sticky secretions in the respiration and digestive tract Mutation in the gene for the transmembrane protein that acts as a channel for chloride ions This gene is located on chromosome #7

Cystic Fibrosis 3,200 white babies born each year with CF 30,000 Americans live with CF 12 million Americans are carriers 1/20 European Americans are carriers http://www.pbs.org/wgbh/evolution/educators/course/session7/explain_b_pop1.html

Cystic Fibrosis & Cholera Cholera produces a toxin that opens chloride channels in the small intestine. This causes the often fatal diarrhea and dehydration in cholera patients. In Europe, cholera epidemics have claimed millions of lives People heterozygous for CF have fewer chloride channels and are resistant to cholera. This explains the prevalence in European Americans

Celine Dion’s niece died of cystic fibrosis Celine Dion’s niece died of cystic fibrosis. Since that time she has been a major spokesperson/fundraiser for cystic fibrosis. Her song, Fly, was written to honor the death of her niece.

Phenylketonuria (PKU) One of the most common causes of mental retardation Mutation in gene for the enzyme phenylalanine hydroxylase on chromosome #12 This enzyme converts the amino acid phenylalanine to the amino acid tyrosine

Phenylketonuria (PKU) If phenylalanine is not broken down, the build up of this amino acid causes brain dysfunction and mental retardation All babies in the US are screen for PKU and if put on a phenylalanine restricted diet will not develop mental retardation. 1 in 4,500 people from Ireland have PKU 1 in 8,000 American Caucasians have PKU The heterozygous condition is believed to give protection against fungal infections in pregnant mothers. The original mutation is believed to be Celtic (northern European) in origin.

Sickle Cell Anemia A blood disorder that results in a change in shape of the red blood cell from round to “sickle” shaped. This causes clogging of capillaries and tissues are deprived of oxygen. Mutation in the beta chain of the hemoglobin protein gene found on chromosome #11.

Sickle Cell Anemia Most prevalent in persons of African descent. 1/12 African Americans are carriers of the disease. Heterozygotes have protection from malaria.

Tay Sach’s Disease A fatal disease that results from the build up of fatty acids around nerves of the central nervous system (brain & spinal cord) Caused by the lack of the enzyme hexosaminidase A which is responsible for degrading lipids (fats) The gene for this protein is located on chromosome #15 Interesting—this enzyme is actually normally found in the lysosomes and is a part of the normal cell recycling system.

Problems Babies appear normal at first. After a few months they develop developmental problems, go blind, deaf, and become paralyzed. They are diagnosed by a “cherry-red” spot in the eye They die by the age of five.

Prevalence Tay-Sachs is most common in descendents of Central & Eastern European Jews About 1/30 American Jews are carriers of Tay-Sachs disease

Autosomal Dominant Disorders Require the inheritance of only one copy of the allele Found on chromosomes 1 - 22

Achondroplasia The most common form of dwarfism Caused by a mutation in the gene for the Fibroblast growth factor receptor 3 protein This protein functions in normal bone growth This gene is found on chromosome #4

Achondroplasia Because dwarfism was widely recorded in Egyptian art, it is considered the oldest recorded birth defect 1/25,000 births result in achondroplasia Over 80% of these births are to parents of normal height; they are the result of a spontaneous mutation It is often hypothesized that the pharoahs were dwarfs—that this rare stature was a sign from the gods.

Huntington’s Disease Genetically programmed degeneration of brain cells causing uncontrolled movements, loss of mental faculties, and emotional disturbance Caused by an abnormal gene for the protein huntingtin. Huntingtin is believed to function in normal brain activity. The gene is located on chromosome #4.

Huntington’s Disease In the normal gene for huntingtin, there is a section of DNA with up to 28 CAG codons repeated. (This codes for glutamine.) In the abnormal gene, there is 40 or more repeats of the CAG codon and subsequently, a longer chain of glutamine in the protein. Chains of glutamine are known for causing other neurological disorders.

Huntington’s Disease Symptoms usually do not appear until a person is in their 40’s There are currently 1,500 people in the US with Huntington’s Disease It affects males and females and all races at the same rate

Marfan Syndrome Characterized by problems with the skeleton, eyes, heart, and blood vessels. Caused by a mutation in the gene for the protein fibrillin. This protein is essential for the formation of elastic fibers in the connective tissue. This gene is located on chromosome #15. Interesting—there is not a single mutation or couple of mutations found in families with this disorder—every family tends to have its “own” mutation.

Marfan Syndrome People with Marfan characteristically are tall with very long limbs and fingers It is believed that Abraham Lincoln had Marfan Syndrome Many times people do not know they have the disease and yet are susceptible to aortic rupture 1/5,000 people in the US have Marfan Syndrome Olympic star volleyball player Flo Hyman died of aortic rupture in 1986. Florida State University basketball player Ronaldo Pierce died of aortic rupture in 2004. Both had Marfan Syndrome.

Neurofibromatosis Results in the growth of noncancerous tumors along nerves Caused by a mutation in the gene for neurofibronin which is believed to act in tumor suppression. Therefore, if it is mutated, tumors are the result. This gene is located on chromosome #17.

Neurofibromatosis People afflicted have tumors that grow on their skin and can have bone deformity 1/4,000 babies in the US are born with neurofibromatosis 30 – 50% of the cases arise spontaneously People usually lead a normal life Interesting---this was once thought to be the disease of the “Elephant Man”. However, now that is diagnosed as Proteus syndrome

Osteogenesis Imperfecta Characterized by bones that break frequently, often from no apparent cause Results from abnormal production of collagen, the protein that is the primary constituent of the connective tissue (BOND IS A CONNECTIVE TISSUE!) The gene for the alpha chain of collagen is located on chromosome #17, and the gene for the beta chain is on chromosome #7. Often referred to as the “brittle bone” disease

Osteogenesis Imperfecta It is estimated there are 20,000 – 50,000 people in the US with OI Many cases are the result of spontaneous mutations The symptoms vary widely but with proper care, good diet, exercise, etc. people with OI can lead normal lives

X-Linked Recessive Females have to inherit two copies of the gene Males have to inherit one copy on the X from their mother

Duchenne Muscular Dystrophy Characterized by progressive muscle weakness and wasting beginning early in life Caused by a mutation in the gene for dystrophin Dystrophin is the structural protein that provides support for muscle cells No dystrophin—muscles do not work

Duchenne Muscular Dystrophy 1/3,500 boys worldwide have DMD Most are wheelchair bound by 10 and die by age 20 Eventually cardiac and respiratory muscles waste away

Fragile X Syndrome Most common cause of genetic mental impairment Mutation in the Fragile X Mental retardation protein believed to help brain cells develop & function normally

Fragile X Syndrome In the promoter region for the FMR1 gene, there are CGG repeats In the normal gene there are 6 – 40 repeats In the abnormal gene there may be hundreds of repeats The more CGG is repeated the more severe the disease Heterozygous females make enough FMR to have normal intelligence 1/2000 males have Fragile X; 1/4,000 females

Fragile X

Hemophilia Disorder resulting in improper blood clotting from cuts or from internal injuries It is a result of a mutation in the gene for Blood Clotting Factor VIII This protein is involved in stopping the flow of blood out of vessels when they are ruptured

ROYAL Hemophilia

Hemophilia About 18,000 people (almost all male) in the US have hemophilia 400 babies in the US each year are born with hemophilia In the 1980’s approximately 10,000 children were infected with HIV because of transfusions for hemophilia With proper treatment, hemophiliacs can live a normal life

Nondisjunction Disorders Caused by an abnormal number of a particular chromosome

Down Syndrome Trisomy 21 Low muscle tone, flat face, slanted eyes, abnormal shape and small size ears Most have congenital heart defects Suffer from mild to moderate mental retardation With good care, most live to around age 55 1/800 to 1/1,000 live births result in Down Syndrome

Down Syndrome

Edward’s Syndrome Trisomy 18 Results in small jaw, low-set ears, malformation of the head, hands, feet; kidney and heart defects 30% of babies die in first month Less than 10% survive first year Occurs in 1/6,000 live births Twice as many females are born with Edward’s as are males

Edward’s Syndrome

Klinefelter’s Syndrome XXY Men affected have enlarged breasts, small testes, sparse facial and body hair, and inability to produce sperm Some have lower IQ, many are very tall with long arms & legs These men live as long as healthy individuals 1/500 – 1/1,000 males in US have XXY 3,000 males are born yearly with XXY

Klinefelter’s Syndrome

Patau Syndrome Trisomy 13 Results in cleft palate, polydactyly, severe mental deficiency, heart defects, and other abnormalities Average lifespan is 3 days Only 1 in 20 children survive longer than 6 months Least common of all survivable trisomies Occurs in 1/8,000 – 1/12,000 births Birth rate favors females

Patau Syndrome

Turner Syndrome Monosomy X Inhibits sexual development and causes infertility Females are usually short with webbed necks, drooping eyelids, bone development problems, and retarded secondary sex characteristics IQ is usually normal Occurs in 1/3,000 live births

Turner Syndrome