Genetics Flashcards
define and give example of codominance
both alleles contribute to phenotype of heterozygote;
ex: Blood groups A, B, AB
define and give example of variable expressivity
phenotype varies among individuals w/ same genotype;
2 pts w/ neurofibromatosis type I (NF1) may have varying disease severity
define and give example of incomplete penetrance
not all individuals w/ mutant genotype show mutant phenotype;
BRCA-1 gene mutations do not always result in breast or ovarian cancer
define and give example of pleiotropy
one gene contributes to multiple phenotypic effects;
PKU causes many seemingly unrelated Sx, ranging from mental retardation to hair/skin changes
define and give example of imprinting
differences in gene expression depend on whether mutation is of maternal or paternal origin;
Prader-Willi and Angelman’s Sx
define and give example of anticipation
increased severity or earlier onset of disease in succeeding generations;
Huntington’s disease
define and give example of loss of heterozygosity
patient inherits/develops a mutation in tumor suppressor gene, complementary allele must be deleted/mutated before cancer develops;
Rb and 2 hit hypothesis
define dominant negative mutation
exerts dominant effect=> heterozygote produces nonfunctional altered protein that prevents normal gene product from functioning
give example of dominant negative mutation
mutation of transcription factor in allosteric site => nonfunctioning mutant bind DNA, preventing wild type transcription factor from binding
define and give example of linkage disequilibrium
tendency for alleles at 2 linked loci to occur together more often than expected by chance => varies in different populations
define a mosaicism
occurs when cells in body differ in genetic makeup due to post-fertilization loss or change of genetic information during mitosis
what is a germ line mosaic?
gonadal that when disease is not carried by parent’s somatic cells
what is a mutation in embryonic precursor of bone marrow stem cell?
hematologic mosaic individual
What is a chimeric individual derived from?
2 zygotes that subsequently fuse
define locus heterogeneity
mutations at different loci can produce the same phenotype
What diseases are associated w/ locus heterogeneity?
Marfan syndrome, MEN 2B, homocystinuria;
all cause marfanoid habitus;
albinism
define heteroplasmy
presence of both normal and mutated mtDNA, resulting in variable expression in mitochondrial inherited disease
define uniparental disomy
offspring receives 2 copies of a chromosome from 1 parent and no copies from the other parent
what does heterodisomy (heterozygous) indicate?
meiosis I error
isodisomy (homozygous) indicates what?
meiosis II error or post-zygotic chromosomal duplication of one of pair of chromosomes;
loss of other original pair
most occurrences of uniparental disomy have how many chromosomes?
correct number of chromosomes w/ normal phenotype
what is the hardy-weinberg population principle? what do the factors mean?
p^2 + 2pq + q^2 = 1=> if p + q=1 then=>
p^2=freq of homozygosity for allele p
q^2=freq of homozygosity for allele q
2pq=freq of heterozygosity (carrier freq w/ autosomal recessive disease)
How can Hardy-weinberg principle be used for X linked diseases?
males = q
females = q^2
what 4 things does the Hardy weinberg law assume?
- no mutation occurring at locus
- no selection for any of genotypes at locus
- completely random mating
- no net migration
define imprinting
at same loci, only 1 allele is active; other inactive by methylation;
1 allele inactivated, deletion of active allele gives disease
What allele is not expressed in prader-willi syndrome?
paternal allele not expressed
what allele is not expressed in angelman’s syndrome?
maternal allele not expressed
what causes prader-willi and angelman’s syndrome?
inactivation or deletion of genes on chromosome 15=> may be result of uniparental disomy
What are Sx of prader willi syndrome
mental retardation; hyperphagia; obesity; hypogonadism; hypotonia
what are Sx of angelman syndrome?
mental retardation, seizures, ataxia, inappropriate laughter
characterize autosomal dominant
due to defects in structural genes => many generations of equal sex affected
What is critical to diagnose autodomal dominant diseases?
family history
characterize autosomal recessive disease
1/4 affected from carrier parents due to enzyme deficiencies usually only 1 generation
characterize XLR genetics
heterozygous mothers have 50% chance of affection w/ no male to male transmission => females must be homozygous to be affected
characterize XLD genetics
transmitted through both parents => male or female offspring affected whereas all female offspring of affected father affected
what is a disease with XLD genetics
hypophosphatemic rickets => vit D resistant rickets resulting in increased phosphate wasting at proximal tubule w/ rickets like presentation
characterize mitochondrial inheritance
transmitted only through mother => all offspring of affected females show signs of disease;
variable expression in population due to heteroplasmy
what are mitochondrial diseases often due to?
failures in oxidative phosphorylation;
how do mitochondrial myopathies present? what are they the result of?
result from mutations affecting mitochondrial function;
present w/ myopathy and CNS disease;
muscle biopsy shows ragged red fibers
what type of disease is achondroplasia? define it
AD;
cell signaling defect of fibroblast growth factor
