Genetics. Summary. HY facts

[FARN]

Genetics. Summary. HY facts

1 Autosomal Dominant
¤Observed in multiple generations of a pedigree
¤Females/Males are affected in roughly equal frequencies
¤No skipped generations
Examples:
ACHONDROPLASIA: prominent forehead, low nasal root, lumbar lordosis. FGFR3 gene (gain of function) -inhibition of bone growth.
¤NEUROFIBROMATOSIS TYPE1 (benign peripheral nerve tumors, cafe-au-lait,
¤NEUROFIBROMATOSIS TYPE 2 - acoustic neromas and cafe-au-lait spots.
¤HUNTINGTON DISEASE - dementia, loss of motor control. Progresses slowly
¤MYOTONIC DISTROPHY - muscle deterioration, cardiac arrhythmia, frontal baldness, testicular atrophy, cataracts

2Autosomal Recessive
¤Seen in only one generation of a pedigree;
¤Occur in heterozygous pairing
E.g.:
CYSTIC FIBROSIS - elevated sweat Cl level, thick mucus in airways, pancreatic insufficiency, absence of ductus deferens, chronic infections
¤HEREDITARY HEMOCHROMATOSIS - absorption of excess iron in the gut. Deposition of Fe in liver (hepatocellular carcinoma, cirrhosis), pancreas, joints.

3X-Linked Recessive
¤Males prevail
¤Heterozygous female with disorder - Manifesting Heterozygote
¤Skipped generations
¤No male-to-male
Examples:
HEMOPHYLIA A, B
DUCHENNE MUSCULAR DYSTROPHY - disorder of dystrophin, that is connected to dystroglycan complex, death from cardiorespiratory failure

4X-Linked Dominant
¤No male-to-male;
¤No skipped generations;
¤twofold more often in females than in males

5Mitochondrial
¤Disease is from affected female
¤Heteroplasmia ¨C when mutation is only in part of mitochondria
EXAMPLES:
¤MERRF (Myoclonic epilepsy,rough rugged fibers)
¤LHON (Leber Hereditary Optic Neuropathy)
¤MELAS (Myoclonic Epilepsy, lactic acidosis, stroke episodes)

Variable Expression (causes):
¤ Environmental Influences;
¤ Types of mutations (missence are less severe than nonsense) ;
¤ Modifier lociCan cause different rates of manifestations: NEUROFIBROMATOSIS 1 AND 2.

Incomplete Penetrance:
¤ Disease ¨C causing genotype has NO manifestations
¤ Obligate carriers -represent skipped generations, offspring are affected.
E.g. HEREDITARY HEMOCHROMATOSIS
When penetrance is given, say A%.
%Affected = %affected(by Mendelian distribution)*%A
%Non-affected = 1 - %affected.

Delayed Age of Onset E.g. HUNTINGTON DISEASE

Pleiotropy:
¤Single disease-causing mutation affects multiple systems
E.G. MARFAN SYNDROME - defective fibrillin

Locus Heterogeneity:
¤The same disease phenotype is produced by mutations in different loci.
E.g. OSTEOGENESIS IMPERFECTA - 17 and 7 chromosome

New Mutation - no comments;

Anticipation:
¤More recent generations have greater severity of disease then preceding generations;
¤Trinucleotide repeat polymorphism expansion within or near the coding gene
MYOTONIC DISTROPHY
FRAGILE X SYNDROME - large ears, enlongated face, hypermobile joints, macroorchidism

Imprinting
¤Different manifestations if inherited from different parents.
Father: PRADER-WILLI - moderate mental retardation, hypogonadism, small hands and feet and obesity
Mother: ANGELMAN - severe mental retardation, seizures, ataxic gait
_ _ _ _ _ _ _ _ _ _ _ __ _ _ _ __ _ _ _ _ _ _ _ _ _ _

GENETIC STATISTICS (short)

Genotype frequency(p2 or q2 or 2 pq): given in Genotype/Count table (genotype: 1,1 and count: 4 thus, gene frequency will be 4/100 = 0,04.
Gene/Allele frequency(p or q): go to table, e.g. Allele frequency for 1 is to be found. Genotype/Count: 1,1;1,2;1,3/4;5;9; Thus, allele frequency is equal to (4+4(for 1,1)+5 (for 1,2)+9(for 1,3))/200 = 0,11

Hardy-Weinberg's
p*p + 2*p*q + q*q = 1 (For X-associated diseases - in males: just p or q (one X only))

Genetic Drift: in small populations frequency of defective genotype increases;
Genetic Flow: mixture of different populations. New genotype is brought to new population.
Natural Selection: Increased frequency of definite genotype in natural environment. AfroAms have more sickle-cell anemia cases.

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ONCOGENES
CLASS/STAGE/PROTEIN ENCODED BY ONCOGENE/ONCOGENE/TYPE OF CANCER/
1 Growth Factor Platelet-derived growth factor sis Astrocytoma, osteosarcoma

2 Receptors Epidermal-growth factor receptor erb B1 sq cell ca of lung

2 Receptors Epidermal-growth factor receptor erb B2 Breast, ovarian, lung and stomach ca

2 Receptors Epidermal-growth factor receptor erb B3 Breast ca

3 Signal transducers Protein tyrosine kinase src Rous avian sarcoma

3 Signal transducers Protein tyrosine kinase abl CML, ALL

3 Signal transducers G prot with guanosine triphosphatase activity ras Abnormal G Protein. Bladder, lung, colon and pancreas ca

4 Nucleal transcription factor Leucine zipper protein fos Finkel-Biskes-Jinkins osteosarcoma

4 Nucleal transcription factor Leucine zipper protein un Avian sarcoma

4 Nucleal transcription factor Helix-loop-helix protein N-myc Neuroblastoma

4 Nucleal transcription factor Helix-loop-helix protein myc Burkitt's ly

4 Nucleal transcription factor Retinoic acid receptor (zinc finger protein) pml/rar §Ò AML

CHROMOSOMES
GENE/DISEASE/COMMENTS
Chromosome 1 ¨CN myc Neuroblastoma Gene Amplification
Chromosome 3 (deletion 3p) AD Von Hippel Lindau Renal Cell CA, Adenomas, Cysts
Chromosome 4 Huntington¡¯s Choreiform movements, (incr number of CAG trinucleotid repeats within HD gene(codes for NMDA receptor) on 4p -AD) Paternal transmission, ANTICIPATION
Chromosome 5 APC Familial Polyposis Coli 100% CA. Suppressor gene (deletion ¨CAD) Gardner¡¯s gets inactivated

Chromosome 6 Hemochromatosis Bronze Diabetes (Mutation in Hfe gene) *HLA genes

Chromosome 7 CF Sweat test, lungs, pancreas (CTFR ¨Cdelta f508: AR, 70% 3-base deletion that codes for phenyl-alanine at position 508) defective Cl ion channel

Chromosome 11 Wilm¡¯s tumor WT1-WAGR Complex, (WT1 and WT2 ¨C 11p) (tumor suppressor gene) hemihypertrophy

Chromosome 13 Wilson¡¯s Disease Corneal Kayser-Fleicher (hepatolenticular) rings, Copper metabolism

Chromosome 13 Retinoblastoma Two-hit. Inactivated tumor (Rb: homozygous del on Osteosarcoma suppressor gene. 13q at bond q14

Chromosome 13 Patau¡¯s (Trisomy)

Chromosome 15 (del15 q11-q13) maternal Angelman¡¯s Microdeletion. MR, burst of laughter

Chromosome 15 (del15 q11-q13) paternal Prader-Willi Microdeletion. MR (mental retardation)

Chromosome 15 Marfan¡¯s Fibrillin gene, AD, ectopia lentis, MVP

Chromosome 16 APKD AD, a/w multiple trinucleotide repeats

Chromosome 17 Pancreatic CA Home of p53
Chromosome 17 Breast CA, Ovarian CA Home of p 53 and BRCA 1 (BRCA 1, 17q and 13q) Normally a suppressor gene

Chromosome 17 NF1 Inactivated tumor suppr gene normally codes for GTPase-act prot that facilitates conversion of active ras-GTP to inactive ras-GTP (NFT 1, 17q: AD)

Chromosome 17 25-50% lung, colon, breast Inactivated tumor suppr gene (p 53, 17p-Guardian of genome)

Chromosome 18 (trisomy) Edward's (Trisomy) Rocker bottom feet micrognathia

Chromosome 21 (Codes for Amyloid precursor protein) Alzheimer's APP gene codes for amyloid precursor protein, a precursor to the A§Ó-peptide

Chromosome 21 Down's (trisomy) simian crease, Brushfield spots

Chromosome 22 Di George Syndrome microdeletion of 22q11, CATCH 22 sy

Chromosome 22 NF2 Bilat acoustic neuroma, meningioma

X-chromosome Fragile X sy Increased number of CGG tandem repeats in the 5' untranslated region of the FMR-1 (flial mental retardation gene

X-chromosome Duchenne mutation in DMD gene located in Xp21 destroys ability of dystrophin to anchor actin to the extracell matrix
Y ¨C SRY- Sex determining. SRY ¨C inhibits DAX-1 locus, which in turn, inhibits male differentiation genes. On crossover event if SRY region moves to X, this may lead to 46XX males.

[Anonymous]

g'luck

[Anonymous]

What"s the source of these high yield facts