Genetic Mutations and Disorders

1. Genetic Mutations and Disorders Biology 30

2. Pedigrees • http://www.youtube.com/watch?v=HbIHjsn5cHo&feature=related

3. Mendelian trait A Mendelian trait is one that is controlled by a single locus and shows a simple Mendelian inheritance pattern. In such cases, a mutation in a single gene can cause a disease that is inherited according to Mendel's laws. Examples include sickle-cell anemia, Tay-Sachs disease, and cystic fibrosis.A disease controlled by a single gene contrasts with a multi-factorial disease, like arthritis, which is affected by several loci (and the environment) as well as those diseases inherited in a non-Mendelian fashion.

4. Sickle cell anemia • http://www.youtube.com/watch?v=9UpwV1tdxcs • http://www.youtube.com/watch?v=-xBvFd2dW4A

5. Non-disjunction disorders. • Non-disjunction is the failure of paired chromosomes or sister chromatids to separate and go to different cells during meiosis.

6. Some disorders with syndromes noted from the Karyotype. • 1. Klinefelter’s syndrome • 2. Turner syndrome • 3. Williams syndrome • 4. Patau syndrome • 5. Edwards syndrome • 6. Cri du chat syndrome • 7. DiGeorge Syndrome • 8. Down’s syndrome

7. For example Klinefelter’s syndrome Klinefelter's syndrome, or XXY syndrome,is a condition in which males have an extra X sex chromosome. Klinefelter'ssyndrome is the most common sex chromosome disorder[2] and the second most common condition caused by the presence of extra chromosomes. The condition exists in roughly 1 out of every 1,000 males. One in every 500 males have an extra X chromosome but do not have the syndrome. The principal effects are development of small testicles and reduced fertility. A variety of other physical and behavioral differences and problems are common, though severity varies and many boys and men with the condition have few detectable symptoms. The syndrome was named after Dr. Harry Klinefelter, an endocrinologist at Massachusetts General Hospital in Boston, Massachusetts, who first described it in 1942. Because of the extra chromosome, individuals with the condition are usually referred to as "XXY Males", or "47, XXY Males”

8. Klinefelter,s karyotype and phenotype

9. TURNER SYNDROME….. Turner syndrome or Ullrich-Turner syndrome encompasses several conditions, of which monosomy X (absence of an entire sex chromosome) is most common. It is a chromosomal disorder in which all or part of one of the sex chromosomes is absent. Typical females have 2 X chromosomes, but in Turner syndrome, one of those sex chromosomes is missing or has other abnormalities. In some cases, the chromosome is missing in some cells but not others, a condition referred to as mosaicism or 'Turner mosaicism'. Occurring in 1 out of every 2500 girls, the syndrome manifests itself in a number of ways. There are characteristic physical abnormalities, such as short stature, swelling, broad chest, low hairline, low-set ears, and webbed necks. Girls with Turner syndrome typically experience gonadal dysfunction (non-working ovaries), which results in amenorrhea (absence of menstrual cycle) and sterility. Concurrent health concerns are also frequently present, including congenital heart disease, hypothyroidism (reduced hormone secretion by the thyroid), diabetes, vision problems, hearing concerns, and many other autoimmune diseases. Finally, a specific pattern of cognitive deficits is often observed, with particular difficulties in visuospatial, mathematical, and memory areas.[

10. Turners karyotype and phenotype

11. Turner Syndrome • http://www.youtube.com/watch?v=66jeP_JrLE0 • http://www.youtube.com/watch?v=_vk2PhaND14

12. Williams syndrome Williams syndrome is a rare genetic condition (estimated to occur in 1/10,000 births) which causes medical and developmental problems. Williams syndrome was first recognized as a distinct entity in 1961. It is present at birth, and affects males and females equally. It can occur in all ethnic groups and has been identified in countries throughout the world. Williams syndrome is caused by the deletion of genetic material from the region q11.23 of chromosome 7. The deleted region includes more than 20 genes, and researchers believe that the loss of several of these genes probably contributes to the characteristic features of this disorder. What are the common features of Williams syndrome? Individuals with Williams syndrome are highly verbal and sociable (having what has been described as a "cocktail party" type personality), but lack common sense and typically have inhibited intelligence. Individuals with WS hyperfocus on the eyes of others in social engagements. Phenotypically, patients tend to have widely spaced teeth and flattened nasal bridge.[ Individuals with Williams syndrome also experience many cardiac problems, commonly heart murmurs and the narrowing of major blood vessels as well as supravalvular aortic stenosis (SVAS). Other symptoms may include many gastrointestinal problems, such as abdominal pain and diverticulitis, as well as hormone problems, the most common being hypercalcemia (elevated calcium levels in the blood). There also appears to be a higher prevalence of left-handedness and left-eye dominance in those with Williams. Individuals with Williams syndrome also report higher anxiety levels as well as phobia development.

13. Williams syndrome

14. Williams syndrome • http://www.youtube.com/watch?v=EgJVTRfwcAU&feature=related

15. Patau’s syndrome Patau syndrome, also known as trisomy 13 and trisomy D, is a chromosomal abnormality, a syndrome in which a patient has an additional chromosome 13. The extra chromosome 13 disrupts the normal course of development, causing heart and kidney defects amongst other features characteristic of Patau syndrome. Like all nondisjunction conditions (such as Down syndrome and Edwards syndrome), the risk of this syndrome in the offspring increases with maternal age at pregnancy, with about 31 years being the average. Patausyndrome affects approximately one in 25,000 live births.

16. Patau syndrome, Trisomy 13, is the least common of the autosomal trisomies, after Down syndrome (Trisomy 21) and Edwards syndrome (Trisomy 18). The extra copy of chromosome 13 in Patau syndrome causes severe neurological and heart defects which make it difficult for infants to survive. The exact incidence of Patau syndrome is not known, although it appears to affect females more than males, most likely because male fetuses do not survive until birth. Patau syndrome, like Down syndrome, is associated with increased age of the mother. It may affect individuals of all ethnic backgrounds. • Extra fingers or toes (polydactyly) • Deformed feet, known as rocker-bottom feet • Neurological problems such as small head (microcephaly), failure of the brain to divide into halves during gestation (holoprosencephaly), severe mental deficiency • Facial defects such as small eyes (microphthalmia), absent or malformed nose, cleft lip and/or cleft palate • Heart defects (80% of individuals) • Kidney defects

17. Edward’s syndrome There are 23 pairs of human chromosomes. In Trisomy 18 (Edwards syndrome), there is an extra chromosome with the 18th pair. Like Trisomy 21 (Down syndrome), Trisomy 18 affects all systems of the body and causes distinct facial features. • Trisomy 18 severely affects all organ systems of the body. Symptoms may include: • Nervous system and brain - mental retardation and delayed development, high muscle tone, seizures, and physical malformations such as brain defects • Head and face - small head (microcephaly), small eyes, wide-set eyes, small lower jaw • Heart - congenital heart defects such as ventricular septal defect • Bones - severe growth retardation, clenched hands with 2nd and 5th fingers on top of the others, and other defects of the hands and feet • Malformations of the digestive tract, the urinary tract, and genitals

18. Cri du chat • Cri du chat syndrome, also known as chromosome 5p deletion syndrome, 5p minus syndrome or Lejeune’s syndrome, is a rare genetic disorder due to a missing part of chromosome 5. Its name is a French term (cat-cry or call of the cat) referring to the characteristic cat-like cry of affected children. It was first described by Jérôme Lejeune in 1963. The condition affects an estimated 1 in 20,000 to 50,000 live births, strikes all ethnicities, and is more common in females by a 4:3 ratio

19. The syndrome gets its name from the characteristic cry of affected infants, which is similar to that of a meowing kitten, due to problems with the larynx and nervous system. About 1/3 of children lose the cry by age 2. Other symptoms of cri du chat syndrome may include: • feeding problems because of difficulty swallowing and sucking. • low birth weight and poor growth. • severe cognitive, speech, and motor delays. • behavioral problems such as hyperactivity, aggression, tantrums, and repetitive movements. • unusual facial features which may change over time. • excessive dribbling. • constipation. Other common findings include hypotonia, microcephaly, growth retardation, a round face with full cheeks, hypertelorism, epicanthal folds, down-slanting palpebral fissures, strabismus, flat nasal bridge, down-turned mouth, micrognathia, low-set ears, short fingers, single palmar creases, and cardiac defects (eg, ventricular septal defect [VSD], atrial septal defect [ASD], patent ductus arteriosus [PDA], tetralogy of Fallot). People with Cri du chat are fertile and can reproduce.

20. Cri du chat

21. DiGeorge Syndrome… DiGeorge Syndrome is a syndrome caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated q11.2 i.e., on the long arm of one of the pair of chromosomes 22. It has a prevalence estimated at 1:4000. The syndrome was described in 1968 by the pediatric endocrinologistAngelo DiGeorge.

22. The features of this syndrome vary widely, even among members of the same family, and affect many parts of the body. Characteristic signs and symptoms may include birth defects such as congenital heart disease, defects in the palate, learning disabilities, mild differences in facial features, and recurrent infections. Infections are common in children due to problems with the immune system's T-cell mediated response that in some patients is due to an absent or hypoplasticthymus. 22q11.2 deletion syndrome may be first spotted when an affected newborn has heart defects or convulsions from lack of calcium due to malfunctioning parathyroid glands and low levels of parathyroid hormone (parathormone). Affected individuals may also have any other kind of birth defect including kidney abnormalities and significant feeding difficulties as babies. Autoimmune disorders such as hypothyroidism and hypoparathyroidism or thrombocytopenia (low platelet levels), and psychiatric illnesses are common late-occurring features.[6]Microdeletions in chromosomal region 22q11.2 are associated with a 20 to 30-fold increased risk of schizophrenia.

23. Individuals with a 22q11.2 deletion can suffer from many possible features, ranging in number of associated features and from the mild to the very serious. Symptoms shown to be common include: • Congenital heart disease (40% of individuals), particularly conotruncal malformations (tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and persistent truncus arteriosus) • submucosal cleft palate, and cleft palate; characteristic facial features. • learning difficulties (90%) but broad range • hypocalcemia (50%)(due to hypoparathyroidism) • renal anomalies (37%) • hearing loss (both conductive and sensorineural) (Hearing loss with craniofacial syndromes) • growth hormone deficiency • autoimmune disorders • seizures (without hypocalcemia) • skeletal abnormalities

24. Down’s syndrome • http://www.youtube.com/watch?v=bEVkbuooXo4