Genetics - Hacia Flashcards
Cytogenetics: What are methods of viewing?
FISH - fluorescent in situ hybridizaion allows viewing of DNA segments SKY - Spectral karyotyping -each chromosome labeled with dif dye array CGH -doesn’t require living cells. uses short DNA probes
Sex chromosome abnormalities
Turner - 45X (found in fetal tissue from miscarriages) Klinefelter - 47 XXY Triple X -47 XXX XYY -47 XYY
Common autosomal chromsomal abnormalities
Down syndrome - trisomy 21 Edwards syndrome - trisomy 18 (eddie walking leash ) Patua syndrome -trisomy 13 (spitting after eating lime)
Diseases from autosomal deletions:
Cri du chat -deletion of chrom 5 arm
diseases from contiguous gene deletion
Small deleted genomic region, contiguous genes. Smith-Magenis -chrom 17 DiGeorge -chrom 22
Genetic mosaicism
cells within person with different genetic makeup ex: nondisjunction during mitosis in development
Irinotecan
Toposiomerase inhibitor. Treat colorectal cancer. (Irene running the tecan, overlooking topography of US)
Oxaliplatin
induces DNA damage. Treat testicular cancer. (Ox destroying DNA on first plate)
5-fluorouracil
antimetabolite. interferes with nucleotide pool.
Telomere disease
Dyskeratosis congenita. Defect in genes for repair and protection of teloeres.
Direct Repair disease
MGMT. repairs O6methyl guanine lesions. Transfers alkyl group at O6 to cysteine residue. MGMT becomes inactivated. loss of MGMT assoc with increase cancer. Tumors related to MGMT deficiency may respond to certain therapies.
Base excision repair disease
FAP2 – familial adenomatous polyposis 2 – risk of colon cancer –mutation in MYH gene
Nucleotide excision repair disease
xeroderma pigmentosa and Cockayne syndrome
mismatch repair disease
• Lynch syndrome- hereditary non-polyposis colorectal cancer HNPCC • Sporadic microsatellite instability colorectal cancer (MSI) – know how to interpret PCR. Microsatellite seq are repetitive dna seq. if mismatch repair defective, ends up with alleles of difference sizes
fanconi anemia
autosomal recessive disorder -mutations in DNA repair genes
missense mutation
alters animo acid identity. eg. CFTR c.1652G>A. p.G551D or p.Gly551Asp
nonsense
converts codon to a stop codon. CFTR cDNA: c.1624G>T Protein: p.G542X or p.Gly542X nonsense mediated decray- destroys mRNAs with premature stop codon
frameshift mutation
insertion or deletion of base pairs, shifts frame and produces premature stop codon. Nonsense mediated decray can degrade mRNA. cDNA: c.3659delC Protein: p.Thr1220LysfsX8 or p.T1220KfsX8
in frame deletion
los of one or more amino acids. open reading frame the same. Nucleotide: c.1521_1523delCTT Protein: p.deltaF508 or p.Phe508del
splice junction mutation
alters sequence identifying site of splicing of intron Nucleotide: 1585-1G>A + or - to designate intron nucleotide
What causes Rett syndrome?
X linked dominant disorder. Males generally not live born. Some males have somatic mosaicism. Caused by MECP2 (methylCpG-binding protein 2) mutations. Only known mutation that causes autism.
Why is BRCA1 and 2 autosomal dominant genes when one has back up normal copy?
Two hit hypothesis: somatic inactivation of backup normal copy in cell along with the inherited mutation.
What disease is caused by CAG triplet repeats in the HTT gene (expansion of polyglutamine) ?
Huntington disease. Severe neurodegenerative disorder. With genetic anticipation-earlier onset in succeeding generations.
What are examples of autosomal recessive disease?
cystic fibrosis, peroxisome biogenesis disorders, Gaucher disease (lysosomal storage disease)
What are examples of x-linked recessive disease?
Duchenne & Becker Muscular Dystrophy Hemophilia
What are peroxisome biogenesis disorders illustrative of?
penetrance- fraction of indivs with a genotype with disease and has symptoms of the disease. Locus heterogeneity- disease or trait caused by mutations at different loci on genes allelic heterogeneity-different mutations at same locus cause same phenotype
compound heterozygous - mutants in the same gene but different inactivating mutations
What inheritance pattern?
Autosomal recessive
autosomal dominant
x linked dominant
x linked recessive
