ZOO405 by Rania Baleela is licensed under a Creative Commons Attribution- NonCommercial-ShareAlike 3.0 Unported LicenseRania BaleelaCreative Commons Attribution- NonCommercial-ShareAlike 3.0 Unported License

This week content Genetic Disorders

1. Sickle Cell Anemia An inherited, chronic disease (monogenic). Cells function abnormally and cause small blood clots. Hemoglobin (Hb) is the O2 carrying protein = 146 AA. People suffering from SCD have different form of Hb.

Sickle cell anemia Glutamic to valine Normal to SCD POINT MUTATION Normal allele: locus 2 in codon 6 Mutant allele: locus 2 in codon 6

2. Cystic Fibrosis (CF) A mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (at 7q31.2). CFTR gene is required to regulate components of sweat, digestive juices and mucus. The most common mutation, ΔF508, is a deletion of 3 bp= loss of AA phenylalanine position 508 on the protein= Affects respiration. Common among Caucasians (1 in 20 are carriers).

Cystic fibrosis has an autosomal recessive pattern of inheritance

3. Down’s Syndrome Individual has a trisomy (3x 21 st chromosomes).

Genetics Trisomy 21, in ~ 94 %, The frequency of trisomy increases with increasing maternal age. Robertsonian translocation involving chromosome 21 in approx. 3-4 %, not related to maternal age. Trisomy 21 mosaicism in 2 to 3 % cases

4. Kleinfelter’s syndrome (or Klinefleter’s) Occurs due to non-disjunction of the X chromosome. The sperm containing both X & Y combines with an egg containing the X, results in a male child (XXY). The egg may contribute the extra X chromosome.

5. Turner’s Associated with underdeveloped ovaries, short stature, and only affects women= one copy of x Individuals are sterile

7. Hemophilia X-linked recessive The oldest known hereditary bleeding disorder. Affects males much more frequently (1 in 10,000) than females (1 in 100,000,000) Patient can bleed to death with small cuts. About 70% of hemophilia patients have <1% of the normal amount and, thus, have severe hemophilia.

A royal disease pedigree chart

8. Huntington’s Disease/chorea autosomal dominant A brain disorder (results in loss of mental and physical control). Caused by the length of a repeated section of a gene exceeding a normal range Chorea means "dance-like movements" and refers to the uncontrolled motions often associated with the disease.

9. Phenylketonuria (PKU) autosomal-recessive hereditary disease Mutations in structure of the phenylalanine hydroxylase gene => deficiency in the hepatic enzyme phenylalanine hydroxylase (PAH)=> Patients cannot consume aspartame.

10. Amyotrophic Lateral Sclerosis (ALS) monogenic mutation A defect on chromosome 21 in the gene encoding superoxide dismutase => protein that is toxic to motor nerve cells is associated with approximately 20% of familial cases of ALS. No known cause in ~95% of cases. Might be caused by environmental pollutants. A common first symptom is a painless weakness in a hand, foot, arm or leg, other early symptoms include speech swallowing or walking difficulty.

11. Albinism X-linked, recessive Patients are unable to produce skin or eye pigments and thus are light-sensitive

12. Achondroplasia (a.k.a. dwarfism) Monogenic, autosomal dominant Caused by the presence of a faulty allele in a person's genome. Achondroplasia is caused by a mutation in the fibroblast growth factor receptor gene 3 (fgfr3). Fgfr3 is an inhibitor that regulates bone growth. In cases of achondroplasia, the fgfr3 gene is too aggressive, negatively impacting bone growth. If 2 alleles are present, the result is fatal.

12. Motor neuron disease

5 diseases 1.Amyotrophic lateral sclerosis (ALS): cause =not known in 90% to 95% of cases. ~5–10% of cases are inherited from parents. ~1/2 of these genetic cases are due to one of two specific genes. Most chromosome Primary lateral sclerosis=> not hereditary in adults and hereditary in juveniles (gene ALS2) 3.Progressive muscular atrophy (PMA) 4.Progressive bulbar palsy=> One form of PBP is found to occur within patients who have a SOD1 mutation 5.Pseudobulbar palsy

PMA