Quiz4_biochem20130928 Flashcards
Features of chromosome behavior
segregation, independent assortment, recombination
Law of segregation
allele pairs separate during gamete formation
principle of independent assortment
alleles of different genes assort & are passed independently of one another from parents to offspring during gamete formation; complicated by linkage
Linkage
tendency of genes located proximal to each other on a chromosome to be inherited together during meiosis
recombination
production of new combinations of alleles encoding a novel set of genetic information (e.g. homologous chromosomal crossing over); any meiotic process generating a haploid product with a genotype differing from that constituted in the meiotic diploid cell
recombinant frequency
total number recombinants/total number progeny; note: independent assortment always produces RF of 50%; RF 50% in test cross indicates that the two genes under study assort independently
LOD score
statistical test for linkage analysis to test whether segregation data from family studies indicates linkage btwn 2 loci or if just due to random segretation
LOD score of 3 or more
indicates linkage, _ at which LOD is highest is the most likely genetic distance btwn the two loci
LOD score of -2 or less
indicates no linkage
Association
co-occurrence of a disease and a genetic marker more often than expected by chance in a population
Linkage vs Association
(1) L must be in families/A can be in unrelated individuals; (2) L is btwn loci/A is btwn specific alleles of loci; (3) A may imply causal/physiological relationship btwn disease and allele/L does not
monogenic genetic disorder
mutation in 1 gene
chromosomal genetic disorder
increase/decrease in copy # of whole chromosomes or chromosomal regions rich in genes
mitochondrial genetic disorder
defects in mtDNA
multifactorial genetic disorder
interplay of multiple genes & multiple environmental factors
somatic genetic disorder
series of genomic changes in somatic cells over time -> not passed to offspring
Product rule
probability of 2 indpendent events occurring simultaneously
Sum rule
probability of either one of the 2 independent events occurring
Autosomal dominant disorder
Normal allele sufficient to compensate for mutant allele; Heterozygotes affected; phenotype appears in every generation (vertical transmission); each child has 50% recurrence risk; males & females equally likely to transmit trait
Gain of fx
mutant gene product has increased or novel activity over normal gene product
Dominant negative
mutant gene product inhibits activity of normal gene product
Haploinsufficiency
half of expression from single normal allele is not nenough protein
Autosomal recessive disorder
both alleles of gene must be defective to cause visible phenotype/disease state; affected individuals homozygous for disease -> both parents must be unaffected heterozygous carriers; if appears in >1 family member typically seen among siblings (horizontal transmission); recurrence risk for each sibling of proband 25%; males & females equally likely to be affected; more common in consanguinity
Loss of fx
inactivation of gene at molecular level
X inactivation
achieves dosage compensation btwn males and females for critical X-linked genes -> transcriptional silencing of one of the X chromosomes in females (DNA methylation)-> Barr body
genes at distal tip of short arm of X chromosome
do not undergo inactivation (up to 15% of genes) -> candidates for clinical phenotype associated with numerical abnormalities of X chromosome
X-linked dominant
few in number; vertical transmission pattern; NO male to male transmission; 2x as common in females
X-linked recessive
females: both copies of X must be defective; males hemizygous for X -> inherit only from mother; gene responsible transmitted from affected man to his daughters -> heterozygous carriers: daughters’ sons have 50% chance of inheriting disease
How can a heterozygous female express an X-linked recessive trait
mosaicism/skewed X-inactivation
Y-linked
no known diseases; expected: male to male transmission, only males affected
Hardy-Weinberg population frequencies
p^2 + 2pq + q^2 = 1; p+q =1
consanguinity
of same kin/mating of related individuals; present more frequently in pedigrees w/ autosomal recessive diseases; increases risk of mating couple both carrying same disease allele