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21 Cards in this Set
- Front
- Back
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Implications of meiosis
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-2 copies of autosomal genes 1 from mom and 1 from dad
-if parent is hetero then ea. kid has a 50/50 chance of getting 1 or the other allele -genes on separate chromos assort independently -when 2 genes are on the same gene they are linked (no indep assortment) -it can be broken by crossing over and also applies to suff other than genes i.e. SNPs restriction polymorphisms,VNTRs |
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Haplotype
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set of linked genes/markers on the chromo (when genes are linked)
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linkage disequlibrium
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-non random assortment b/t 2 alleles on the chromo
-linkage focuses on a locus -diseq. focuses on an allele |
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Single gene disorders
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-disease causing alleles arise in new germline mutations
-if dominant, cause disease immeadiatley after they arise - if severely dominant natural selection removes -Recessive are time bombs -they are carried through generations un-noticed then cause disease in a homozygote -natural selection ignores them if a heterozygote and allow them to be common |
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AD inheritence
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- pt.s are heterozygotes
-male and female are affected equally -their kids have a 50/50 risk of getting disease -affected offspring have affected parents -disease doesn't skip gens - unaffected people don't carry the gene -rare for 2 heterozygotes to meet -new mutations are common and dec penetrance -severe dominant mutations are caused by new mutations |
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Achondroplaisa
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-AD,single gene
-linkage ocan be found on chromo 4 and 12 -1:10,000; 80-90% new mutations -allelic heterogeneity -Point mutation in FGF receptor 3 (FGFR3) expressed in chondrocytes -Trait shows full penetrance and little variability -paternal age increases risk for new mutations Symptoms: -dysmorphic dwarfism -short limbs -lumbar lordosis -prominant forehead -norm trunk -small nose/low nasal bridge -homozygotes die @ birth Problems w/ counsiling: ACH homozygotes or ACH/HCH compound heterozygotes are as badly off as TD patients the most common form of short-limbed dwarfism |
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Aperts
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-1:10000
-mutations in the gene for fibroblast growth factor receptor (FGFR2) -Craniosynostosis (abnormal fusion or cranial structures) -AD -Mental deficiency -hearing loss -syndactyly -cardiac septal problems |
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Hypochondroplasia
(HCH) |
-AD
-Often inherited Mutations in FGFR3 gene -Allelic heterogeneity -prominant forehead -hypoplaisa of mid face -norm body size -small hands -norm intelligence -narrowing of spinal canal |
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Thenatophoric dysplasia (TD)
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-AD
-All cases of TD are result of new mutations in FGFR3 gene -Allelic heterogeneity -Misshapen head -severe platyspondylia -almost always results in neonatal death -narrowing of spinal canal -very short ribs |
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Duchenes Muscular Dystrophy
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-XR
-1/3 cases involve new mutations -1:4000 male births 60% due to deletions one of the dystrophin gene largest genes characterized of the X chromosome should be high in skeletal and cardiac muscle -Maintains muscle membrane structure -Mutations in the Dystrophin gene partial deletions most common with a variety of point mutations -early childhood onset -muscle wasting starting at 1-2 years -wheelchair bound by 10-12 years -die by 16-20years due to respiratory cardiac failure -characteristic is Large fatty calves -dx by deletion scanning oe linkage,PCR,Southern Blot,inc Creatine kinase -females have an inc risk and have more musc weakness - |
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Ohter muscular diseases
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Beckers:
-XR -mild mut. in dystrophin gene Limb girdle: -AR gene products interact w/ dystrophin |
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Skewed X chromosome inactivation
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-carriers of an X linked disease will show symptoms if X inactivation is skewed or have more of 1 parents X active
-reasons for skewing are random -can be local so symptoms are seen in only 1 tissue/region -one X has a deletion which leads to cell death in the cells that have this chromo active -is also caused by inactivation of translocated autosomal material that causes cell death -X inactivation doesn't spread through nautosomal material |
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Anticipation
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-genetic diseases that show an earlier age of onset and more severe expression in the more recent generation of a pedigree
-occurs in triplet repeat disease b/c inc # of repeats leads to a more sev. phenotype/earlier onset -the repeat # inc in meiosis only or mostly in 1 sex |
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Trinucleotide repeats
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-natural occuring seq in 3 bp's that are repeated
-probs happen when these are long -if above the length sequences become unstable and lead to a premutation -also the exp. or fnx of the product changes leading to a full mutation w/ symptoms -can determine length by PCR (could be too big) or Southern blot |
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Other triplet diseases
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-most have CAG repeats in the exon
-dystrophia myotonic has a CTG repeat is AD -Fredreich ataxia has GAA repeat in intron AR -fragile X has CGG repeat X linked |
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Huntingtons
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-AD
-1:20,000 -CAG trinucleotide repeat expansion in genes coding for glutamines called huntingtin -10-30 CAG repeat is normal 36-121 causes HD -Fragment of protein precipitates binding inhibitors of histone acetylation -anticipation occurs -neurodegenerative disorder -progressive -personality change -memory loss -involuntary motor problems -early onset when disease is inherited paternally -37 years is usual age of onset but 100% penetrance by 80 years old -earlier onset/more severe phenotype when repeat number increases -homozygotes and heterozygotes equally affected l -lowest mutation rate of any known locus (for repeats under 20)Woody Guthrie |
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Myotinic dystrophy
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-1 in 10,000
-AD w/ anticipation -Tandem Repeat Expansion - CTG amplification at the 3’ gene for myotonin kinase -normal individuals show 5-30repeats -Myo Dys 50-1000 repeats -if more than 50 in females then is unstable=anticipation -wasting of sternomastoid and facial musc. and distal limb musc -cataracs -cardiac arrythmias -variable severity - |
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Fragile X
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-1:2000 male births
-cytogenic fragile site on X chromosome -unstable CGG trinucleotide repeats in the 5’of the FMR1 gene (upstream of start site) -FMR1 becomes hypermethylated and transcription is suppressed -usually occurs during -female meiosis -exclusively repeat expansion when inherited through mother -males carrying more than 230 repeats are affected with increasing severity (up to 2000) -female carriers that carry full mutation dec IQ. |
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Fragile X symptoms
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-moderate to severe mental retardation (variable)
-Big ears -Prominent jaw -High pitched speech -Protruding forehead -Coarse facial features -Unusually large testis -Most common form of moderate mental retardation |
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Complications w/ gene expressivity
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-incomplete penetrence: pt. has genotype for disease but dosen't show the phenotype, kids can be affected i.e. retinoblastoma
-variable expression: shows penetrence, but severity differs greatly,a parent can have a mild exp. and kid can have a bad exp. |
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Continued
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-Locus heterogeneity:mutations in diff genes causes same phenotype,1 disease pheno can be caused by muts in diff loci in diff families
-allelic heterogeneity: variable exp cand be caused by diff types of muts at the same disease locus(diff muts in the same gene -phenocopies: conditions that look like genetic diseases but are caused by nongenetic factors -pleiotropy: genes that have more than 1 effect on the body i.e marfan,CF Imprinting: differential activation of genes depending on which parent they came from ,several genes in a critical region are active on 1 chromo if the active copy is deleted b/c of mut. then disease occurs -contiguous disorders: some syndromes involve the deletion of adjacent genes to those of the disease,micro del and micro duplication |
