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37 Cards in this Set
- Front
- Back
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what are the exceptions to the rule for autosomal dominant inheritance?
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new mutations
variable expressivity penetrance mosaicism (somatic or germline) age of onset nonpaternity |
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when indicates a new mutation?
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*no fam history of disease
*mutation happened in either sperm or egg, so every cell in patient has mutation *neither parent has mutation in their other cells and thus is not affected |
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what are some exs of new mutations?
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1) diastrophic dysplasia
2) osteogenesis imperfecta: type II *perinatal lethal *have severe bone and cartilage abnormalities |
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what is most severe type of osteogenesis imperfecta?
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II
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what are symptoms of osteogenesis imperfecta II?
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large, unmineralized skull
small thoracic cavity long bones of arms and legs are short and deformed vertebral bodies flattened all bones undermineralized |
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what does it mean for a gene to have pleiotropic effects?
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genes that affect multiple organ systems
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what is char of variable expressivity?
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great variability in phenotypic expression of disease
*even w/i fam, individuals who have same disease mutation may have different clinical manifestations of disease *esp common in genes w/ pleiotropic effects |
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what may be causes of variable expressivity?
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environmental influences and/or effect of other genes that modify expression of mutant gene
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what's difference in question that variable expressivity and penetrance ask?
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variable expressivity: which form of disease do you have?
penetrance: is the disease present or not? |
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what are some exs of auto dom diseases w/ variable expressivity?
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Waardenburg Syndrome
Neurofibromatosis I Marfan ectrodactyly Van der Woude syndrome |
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what are ways that waardenburg syndrome may be expressed?
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*dystopia canthorum: lateral displacement of canthi
*heterochromia iridium (2 diff color eyes) *high, broad nasal root *confluent eyebrows *white forelock *congenital deafness |
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what are char of penetrance?
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if nonpenetrant: individual carries copy of disease gene, but does not appear to have disease phenotype
*any disorder that doesn't cause ppl to always have it if they have the gene is said to have reduced penetrance |
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if a person w/o symptoms for auto dom disease has both parent and child w/ disease, what are they called?
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obligate heterozygote
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what's the risk of offspring having disease of a nonpenetrant, obligant gene carrier (has disease gene, but not disease symp)?
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risk = 1/2 (penetrance %)
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what's an ex of an auto dom w/ reduced penetrance?
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ectrodactyly: split-hand deformity
Van der Woude syndrome |
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how can auto dom disease Van der Woude syndrome be shown?
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reduced penetrance
variable expressivity |
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what are possible symp of Van der Woude syndrome?
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lip pits
bilateral cleft lip and palate |
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what is somatic mosaicism?
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individual or tissue that has genetically distinct pops of somatic cells
*2 or more cell lines that are genetically diff from single zygote *mutations in single cell some time after fertilization |
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what is major cause of cancer: somatic mutations or germline mutations?
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somatic mutations
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what's an ex of somatic mosaicism?
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McCune Albright syndrome
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what are char of germline mosaicism?
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*if mutation happens in individual's gametes, varying proportions of gametes carry mutant disease allele
*if fam has more than 1 affected child w/ rare mutation, then 1 parent may have germline mosaicism |
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how common are mutations?
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*rare! 1 in 10^4 or 10^6
*highly unlikely for 2 mutations to occur independently in same family |
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is the percent chance of germline mosaicism the same for every disease?
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no- differs
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what are diseases that are caused by germline mosaicism?
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NF-1
achondroplasia Duchenne Muscular Dystrophy Hemophilia A |
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what are factors affecting NF1 inheritance?
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germline mosaicism
variable expressivity |
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what are possible symptoms in NF1?
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*multiple benign fleshy tumors in skin
*multiple flat irregular pigmented skin lesions: cafe-au-lait spots *small benign tumors (hamartomas) on iris: Lisch nodules less common: *mental retardation *CNS tumors *cancer of nervous system or muscle |
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when can somatic and germline mosaicism coexist in same individual?
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if mutation occurs during embryogenesis
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when can mosaicism be passed on to next generation?
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if occurs before separation of germline from somatic cells in fetus
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what auto dom disorders manifest itself at an older age?
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Huntington disease
Polycystic Kidney Disease Alzheimer Disease (PS1, PS2, APP) Breast Cancer (BRCA1, BRCA2) |
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is it common to be heterozygous or homozygous for auto dom disorder?
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hetero
if homozy- more severe phenotype |
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if someone is homozy for the auto dom disorder, how many of their kids inherit the disease gene?
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100%
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what are exs of auto dom where homozygosity is lethal in utero?
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achondroplasia
Marfan syndrome |
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what's diff b/w hetero and homozy ppl w/ familial hypercholesterolemia?
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hetero- really high cholesterol
homozy- ridiculously high cholesterol a lot sooner |
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what are symp of familial hypercholesterolemia?
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*premature heart disease from atheromas (deposits in coronary aa)
*xanthomas: deposits in skin and tendons *arcus corneae: deposits around cornea |
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how does homozygosity and heterozygosity affect ppl w/ huntington disease?
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homozy and hetero have similar age at onset, similar symp and similar disease progression
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what's sex limited inheritance? ex?
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autosomal disorders: gene influencing disorders is not on sex chromos ; gene is on one of autosomes
*phenotype only expressed in hetero and homozy of one gender ex: breast cancer or male pattern baldness |
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why don't women experience male pattern baldness for the most part?
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reduced penetrance in females
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