Genetic Disorders

Inheritance of Genetic Traits Genetic Disorders Inheritance of Genetic Traits www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Brief History First there was Gregor Mendel, a monk who studied inherited characteristics. This was followed by Francis crick and James Watson who unraveled the DNA molecule. This has led us to understanding the human genome sequence www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Gregor Mendel 1866 Gregor Mendel published the results of his investigations of the inheritance of "factors" in pea plants. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Rosalind Franklin 1950's. Maurice Wilkins (1916- ), Rosalind Franklin (1920-1957), Francis H. C. Crick (1916- ) of Britain and James D. Watson (1928- ) of the U.S. Discover chemical structure of DNA, starting a new branch of science--molecular biology. . www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Watson and Crick Watson and Crick made a model of the DNA molecule and proved that genes determine heredity www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Arthur Kornberg 1957 Arthur Kornberg (1918- ) of the U.S. produced DNA in a test tube. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Genetic code 1966 The Genetic code was discovered; scientists are now able to predict characteristics by studying DNA. This leads to genetic engineering, genetic counseling. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Barbara McClintock 1983 Barbara McClintock (1902-1992) of the U.S. was awarded the Nobel Prize for her discovery that genes are able to change position on chromosomes. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

DNA Fingerprinting The late 1980's. An international team of scientists began the project to map the human genome. The first crime conviction based on DNA fingerprinting, in Portland Oregon. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Gene Therapy 1990. Gene therapy was used on patients for the first time. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Dr. Kary Mullis                             1993 Dr. Kary Mullis discovered the PCR procedure, for which he was awarded the Nobel prize. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

DNA Testing                             1995. DNA testing in forensics cases gains fame in the O.J. Simpson trial. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Cloning Begins 1997. Dolly the sheep - the first adult animal clone.                                       1997. Dolly the sheep - the first adult animal clone. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Human Genome Project Imagine a world in which we will be able to treat diseases by altering our very genes‚ giving us new ones if ours are non-functional, changing bad genes for good ones. For the first time in our existence, we are closer to understanding just what we are. We now have the tools to make the whole world better through science ‚ the science of the human genome. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Mutations Gene mutations can be either inherited from a parent or acquired. A hereditary mutation is a mistake that is present in the DNA of virtually all body cells. Hereditary mutations are also called germ line mutations because the gene change exists in the reproductive cells and can be passed from generation to generation, from parent to newborn. Moreover, the mutation is copied every time body cells divide www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Mutations occur all the time in every cell in the body Mutations occur all the time in every cell in the body. Each cell, however, has the remarkable ability to recognize mistakes and fix them before it passes them along to its descendants. But a cell's DNA repair mechanisms can fail, or be overwhelmed, or become less efficient with age. Over time, mistakes can accumulate. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

extra, missing or mixed up chromosomes Mistakes in Meiosis extra, missing or mixed up chromosomes

Autosomal Aneuploidy having an unusual number of chromosomes 1-22 usually fatal Trisomy – have three of a particular autosome instead of just two results from nondisjunction (homologous chromosomes fail to separate) Examples: 1. trisomy 8 2. trisomy 13 (Patau syndrome) 3. trisomy 18 (Edward syndrome) 4. trisomy 21 (Down syndrome)

How to Study aneuploidy: take sample cells from fetus & photograph metaphase chromosomes – line them up according to length & location of centromere = karyotype

Trisomy 13 Patau’s Syndrome An individual with full trisomy 13 at age 7 years (survival beyond the first year is uncommon).  He is deaf and legally blind

Edward’s Syndrome trisomy-18 1/8000 live births Possible Malformations: * Back part of head may be prominent * Short eyelids * Small mouth and unusually small jaw * A small head * Fold of the eyelid in the lateral corner of the eye * Low set malformed ears

Trisomy-21 Three chromosomes in the 21st pair, and 47 total chromsomes Also called Down Syndrome Leads to physical defects and mental retardation http://learn.genetics.utah.edu/content/disorders/whataregd/down/index.html

(Down Syndrome) Trisomy 21 Decreased muscle tone at birth Separated sutures (joints between the bones of the skull) Asymmetrical or odd-shaped skull Round head with flat area at the back of the head Small skull Upward slanting eyes Small mouth with protruding tongue (see tongue problems) Broad short hands Single crease on the palm (see below) Retarded growth and development Delayed mental and social skills (mental retardation) http://www.wayzata.k12.mn.us/cms/images/stories/academics/7th%20Grade/7%20Blue%20Science/genetics-human_gen.ppt

Down’s Syndrome Caused by non-disjunction of the 21st chromosome. This means that the individual has a trisomy (3 – 2lst chromosomes). www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Down’s Syndrome or Trisomy 21 www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Symptoms of Down Syndrome Upward slant to eyes. Small ears that fold over at the top. Small, flattened nose. Small mouth, making tongue appear large. Short neck. Small hands with short fingers. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Symptoms of Down Syndrome Low muscle tone. Single deep crease across center of palm. Looseness of joints. Small skin folds at the inner corners of the eyes. Excessive space between first and second toe. In addition, down syndrome always involves some degree of mental retardation, from mild to severe. In most cases, the mental retardation is mild to moderate. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

sex chromosome aneuploidy missing or extra sex chromosome(s) Examples: 1. Turner Syndrome - XO  females who lack ovaries & sex characteristics; short & sterile 2. Klinefelter Syndrome - XXY  taller, longer limbs, sterile, some exhibit mental retardation 3. XYY male – 1 in every 1000; normal, fertile, taller than average

Turner Syndrome - XO http://learn.genetics.utah.edu/content/disorders/whataregd/turner/

Turner’s Turner syndrome is associated with underdeveloped ovaries, short stature, webbed, and is only in women. Bull neck, and broad chest. Individuals are sterile, and lack expected secondary sexual characteristics. Mental retardation typically not evident. Chromosomal or monogenic? www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Turner’s Syndrome www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Klinefelter Syndrome - XXY http://learn.genetics.utah.edu/content/disorders/whataregd/klinefelter/

Kleinfelter’s syndrome (or Klinefleter’s) Disorder occurring due to nondisjunction of the X chromosome. The Sperm containing both X and Y combines with an egg containing the X, results in a male child. The egg may contribute the extra X chromosome. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

XXY Males with some development of breast tissue normally seen in females. Little body hair is present, and such person are typically tall, have small testes. Infertility results from absent sperm. Evidence of mental retardation may or may not be present. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

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XYY male Two men, one taller than the other. (c) Dorling Kindersley

A. Dominant Autosomal Heredity Huntington’s disease – a rare genetic disorder caused by a dominant gene  progressive degeneration of the nervous system causes uncontrolled jerky movements & mental deterioration  no effective treatment exists  passed on because symptoms don’t occur until 30-50, after they have children  if you are at risk, you can find out if you are a carrier with a biochemical test http://learn.genetics.utah.edu/content/disorders/whataregd/hunt/index.html

Huntington’s Disease Huntington's disease (HD) is an inherited, degenerative brain disorder which results in an eventual loss of both mental and physical control. The disease is also known as Huntington's chorea. Chorea means "dance-like movements" and refers to the uncontrolled motions often associated with the disease. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

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Huntington’s Looking back at the pedigree chart is Huntington’s dominant or recessive? Scientists have discovered that the abnormal protein produced by the Huntington's disease gene, which contains an elongated stretch of amino acids called glutamines, binds more tightly to HAP-1 than the normal protein does. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Huntington's disease (HD) may be rare but among those who grew up in the '60s this disease is well known --- folk singer Woody Guthrie died at age 55 from the genetic disorder. Guthrie was the father of the well-known peace-and-love era hippie singer-songwriter Arlo Guthrie most famous for Alice's Restaurant. Woody Guthrie inherited the progressive neurodegenerative disease from his mother and passed it on to two of his children. Their slow fatal declines were described by their caregiver as "a descent into hell." With the onset of HD a patient suffers years of physical and mental deterioration with attendant psychiatric problems leading eventually to death. Because HD is a dominant genetic disease, children with an affected parent have a 50/50 chance of inheriting the fatal genetic disorder. Read more: http://www.digitaljournal.com/article/287977#ixzz3XWMZGfyy http://www.digitaljournal.com/article/287977 www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

B. Recessive Autosomal Heredity most genetic disorders caused this way; rare except in some ethnic groups

1. cystic fibrosis most common lethal genetic disorder among Americans 1 in 20 carry the recessive allele; 1 in 2000 has it thick mucous in lungs makes breathing difficult; frequent lung infections thick mucous also slows the secretion of some digestive enzymes physical therapy, special diets, & new drug therapies have raised average life span http://learn.genetics.utah.edu/content/disorders/whataregd/cf/index.html

Physiotherapy for cystic fibrosis sufferer. (c) Dorling Kindersley

2. sickle-cell anemia a blood disorder most common in black Americans (Africa) or white Americans (Mediterranean Sea) red blood cells are shaped like a sickle or half moon – can clog blood vessels  rbc’s have a shorter life span – people suffer from anemia hemoglobin protein in these cells differs from normal by one amino acid treatments include transfusions & drug therapy hetero’s can show signs if oxygen availability is low http://learn.genetics.utah.edu/content/disorders/whataregd/sicklecell/index.html

Cystic Fibrosis (CF) Monogenic Cause: deletion of only 3 bases on chromosome 7 Fluid in lungs, potential respiratory failure Common among Caucasians…1 in 20 are carriers Therefore is it dominant or recessive? www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Sickle Cell Anemia An inherited, chronic disease in which the red blood cells, normally disc-shaped, become crescent shaped. As a result, they function abnormally and cause small blood clots. These clots give rise to recurrent painful episodes called "sickle cell pain crises". www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Sickle Cell Sickle cell disease is most commonly found in African American populations.  This disease was discovered over 80 years ago, but has not been given the attention it deserves. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

3. Tay-Sachs disease affects the nervous system missing an enzyme that normally breaks down a lipid produced & stored in the central nervous system & it accumulates in the cells results in blindness, progressive loss of movement & mental deterioration symptoms occur within the first year of life & result in death by age 5; no treatment allele common in PA Dutch http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002390/

Tay-Sachs disease Monogenic, autosomal recessive Central nervous system degrades, ultimately causing death. Most common among people of Jewish, eastern Europe descent. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

4. phenylketonuria is a treatable genetic disorder (Norway, Sweden) absence of an enzyme that converts one amino acid, phenylalanine, to tyrosine phenylalanine accumulates & can cause severe damage to the central nervous system newborns appear normal since mother’s normal enzyme level prevents accumulation, but when newborn begins drinking milk (high in phenylalanine) accumulation begins PKU tests are now preformed on all newborns a few days after birth to prevent retardation http://learn.genetics.utah.edu/content/disorders/whataregd/pku/index.html

Phenylketonuria or PKU People with PKU cannot consume any product that contains aspartame. PKU is a metabolic disorder that results when the PKU gene is inherited from both parents (recessive or dominant? Monogenic or chromosomal?) Caused by a deficiency of an enzyme which is necessary for proper metabolism of an amino acid called phenylalanine. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

PKU Phenylalanine is an essential amino acid and is found in nearly all foods which contain protein, dairy products, nuts, beans, tofu… etc. A low protein diet must be followed. Brain damage can result if the diet is not followed causing mental retardation…and mousy body odor (phenylacetic acid is in sweat). www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

PKU www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Phenylalanine. Free diet www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Even More Genetic Disorders:

Achondroplasia (dwarfism) Symptoms Absent or delayed sexual development in an adolescent Excessive thirst with excessive urination Headaches Increased urine volume Short stature -- below 5th percentile on a standardized growth chart, an adult less than 5 feet tall Slow growth before age 5 Slowed or absent increase in height Short person with short limbs, with large head and prominent forehead. (c) Dorling Kindersley

Achondroplasia (a.k.a. dwarfism) Monogenic, autosomal Carriers express genes, therefore, is it dominant or recessive? There is also a disease called gigantism (Andre the Giant) www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Fragile X Syndrome Overview Fragile X syndrome is a genetic condition involving changes in part of the X chromosome. It is the most common form of inherited mental retardation in males and a significant cause of mental retardation in females. Symptoms Mental retardation Large testicles (macro-orchidism) after the beginning of puberty Large body size Tendency to avoid eye contact Hyperactive behavior Large forehead or ears with a prominent jaw Grey haired man with prominent chin. (c) Dorling Kindersley

Albinism Albinism is a congenital absence of normal pigmentation. It is characterized by partial or total lack of melanin pigment in the eyes, skin and hair. People who have this condition have visual difficulties like hypersensitivity to bright light and glare and many others.

Albinism Patients are unable to produce skin or eye pigments, and thus are light-sensitive Autosomal recessive Therefore, is it monogenic or chromosomal? www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Galactosemia http://learn.genetics.utah.edu/content/disorders/whataregd/galactosemia/index.html

Cri-du-Chat Symptoms Cry that is high-pitched and sounds like a cat Downward slant to the eyes Low birth weight and slow growth Low-set or abnormally shaped ears Mental retardation Partial webbing or fusing of fingers or toes Single line in the palm of the hand (simian crease) Skin tags just in front of the ear Slow or incomplete development of motor skills Small head (microcephaly) Small jaw (micrognathia) Wide-set eyes http://learn.genetics.utah.edu/content/disorders/whataregd/cdc/index.html

Williams Syndrome Williams syndrome is a rare genetic disorder that can lead to problems with development affects a child's growth, physical appearance, and cognitive development missing genetic material from chromosome 7, including the gene elastin - gives blood vessels the stretchiness and strength The most common symptoms of Williams syndrome are mental retardation, heart defects, and unusual facial features (small upturned nose, wide mouth, full lips, small chin, widely spaced teeth). People with this syndrome also exhibit characteristic behaviors, such as hypersensitivity to loud noises and an overly outgoing personality. http://learn.genetics.utah.edu/content/disorders/whataregd/williams/index.html

Resources: http://www.biology.iupui.edu/biocourses/N 100/humgenetics2.html http://biologyexams4u.blogspot.com/2012/ 03/human-genetic-disorder-part-i.html http://www.warrenhills.org/Page/4382 Genetic Disorders narragansett.k12.ri.us/NHS PowerPoint Genetic Disorders faculty.ccc.edu/jminarcik/Ch5.ppt

Hemophilia, the royal disease Hemophilia is the oldest known hereditary bleeding disorder. Caused by a recessive gene on the X chromosome. There are about 20,000 hemophilia patients in the United States. One can bleed to death with small cuts. The severity of hemophilia is related to the amount of the clotting factor in the blood. About 70% of hemophilia patients have less than one percent of the normal amount and, thus, have severe hemophilia. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

X-linked Inheritance pedigree chart www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Color Blindness Cause: x-linked recessive 1/10 males have, 1/100 females have. Why the difference? Individuals are unable to distinguish shades of red-green. Are you color blind?                                            www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

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Muscular Dystrophy What Is Muscular Dystrophy? Muscular dystrophy is a disease in which the muscles of the body get weaker and weaker and slowly stop working because of a lack of a certain protein (see the relationship to genetics?) Can be passed on by one or both parents, depending on the form of MD (therefore is autosomal dominant and recessive) www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

ALS (Amyotrophic Lateral Sclerosis, or Lou Gehrig’s disease) www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

the disease strikes people between the ages of 40 and 70, and as many as 30,000 Americans have the disease at any given time This monogenic mutation is believed to make a defective protein that is toxic to motor nerve cells. A common first symptom is a painless weakness in a hand, foot, arm or leg, other early symptoms include speech swallowing or walking difficulty www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Adenoleukodystrophy ALD) is a rare, inherited metabolic disorder that afflicts the young boy Lorenzo Odone, whose story is told in the 1993 film 'Lorenzo's oil'. In this disease the fatty covering (myelin sheath) on nerve fibers in the brain is lost, and the adrenal gland degenerates, leading to progressive neurological disability and death. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Lorenzo’s Oil Their invention, Lorenzo's Oil, has been adopted as the therapy of choice for ALD by major neurological institutes the world over. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Lorenzo Odone The oil came too late to stop his son from developing the symptoms must be hard to bear. Lorenzo lost most of his bodily functions and has been bedridden for 18 years. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Diabetes Disease in which the body does not produce or properly use insulin. Insulin is a hormone that is needed to convert sugar, starches, and other food into energy needed for daily life. Genetic mutation can lead to Type 1 diabetes, but no one sure if relative to a specific gene www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Diabetes Warning signs Type 1 reveals itself in childhood, Type 2 can be made worse from excessive lifestyle Warning signs Extreme thirst Blurry vision from time to time Frequent urination Unusual fatigue or drowsiness Unexplained weight loss Diabetes is the leading cause of kidney failure, blindness, and amputation in adults, and can also lead to heart disease. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

The very tragic disease… hairy ears Y-linked trait, which are rare symptoms…hairy ears Only 1 cure known…. www.narragansett.k12.ri.us/NHS/.../mrreis/.../Genetic%20Disorders.ppt

Summary of Genetic Disorders http://www.meddean.luc.edu/lumen/MedEd/USMLE/Table_of_Genetic_Disorders.pdf