Unit 2 Day 4 Flashcards
What is AD?
mutation rate
What is AR?
carrier rate
population genetics
the study of allele frequencies and changes in allele frequencies in populations
mutation rates
a measure of the rate at which various types of mutations occur over time. Mutation rates are typically given for a specific class of mutation, for instance point mutations, small or large scale insertions or deletions.
fitness
individual reproductive success and is equal to the average contribution to the gene pool of the next generation that is made by an average individual of the specified genotype or phenotype.
consanguinity
the property of being from the same kinship as another person. In that aspect, consanguinity is the quality of being descended from the same ancestor as another person.
hardy Weinberg principle
allele and genotype frequencies in a population will remain constant from generation to generation in the absence of other evolutionary influences.
population genetics
the study of allele (mutation) frequencies and changes in allele (mutations) frequencies in populations
-we are interested in deleterious mutations and a few beneficial ones
what are population genetics important for?
understanding allele frequency in populations and how those frequencies change
population sampling by phenotype leads to what?
estimates of allele frequency the underlying genetic mechanism
what are the basic principles of population genetics?
estimate mutation rates
determine fitness
effects of consanguinity
addition of new mutations to gene pool
hardy weinberg frequency
p+q=1
hardy weinberg equation
p² + 2pq + q² = 1
what is q in the hardy weinberg equation
q equals all of the alleles in individuals who are homozygous recessive (aa) and the other half of the alleles in people who are heterozygous (Aa)
what is p in the hardy weinberg equation
p equals all of the alleles in individuals who are homozygous dominant (AA) and half of the alleles in people who are heterozygous (Aa) for this trait in a population.
what can we learn from hardy weinberg principles?
- new mutations occur regularly
- most mutations are benign
- next gen DNA sequencing will determine whether the estimates we derive of mutation rates are correct
- by observing the number of cases of disease in a pop, it is possible to calculate rates of mutation for diff conditions
Assumptions of Hardy Weinberg principle
population matings are random
allele frequencies remain constant over time
why do allele frequencies remain constant over time?
- No appreciable rate of mutation
- All genotypes are equally fit (equal chance to pass alleles to next generation)
- No significant immigration/emigration of individuals with different allele frequencies
allele frequency estimation is useful for?
- autosomal recessive where you estimate carrier rates
- applied genetic counseling for couples (integrate family history)
what is the carrier frequency
2pq
what is prevalence of disease
q^2
why sex?
allows introduction of genetic variation to propagate new genetic traits
-benefits organisms who live in changing env., need to fend off disease, need to purge deleterious mutations
variation occurs due to ?
parental genomes
recombination in meiosis
sexual dimorphism
phenotypic differences btw males and females
reproductive organs, body habitus
Jacob’s syndrome
47, XYY learning disabilities speech delay developmental delay behavioral/emotional difficulties autism tall 1/1000 boys
Triplet X syndrome
47XXX tall risk of: learning disabilities, delayed speech delayed motor milestones seizures kidney abnormalities 1/1000 newborn girls
gonad determination is…?
chromosomal
-y=male
-x and no y=female
(normal cases)
are fetuses inherently female?
no.
both ovaries/testes result from common, bipotent gonad
gene directed processes
what do the gonads tell the body to develop?
secondary sex charachteristics
phenotypic features
genital ducts
2 in males and females
mesonephric/wolffian ducts=male structures
paramesonephric/mullerian ducts=female structures
Mesonephric/Wolffian ducts
-SRY on Y chromosome; SOX9 gene
(transcription factors produce MIS, regression of paramesonephric ducts)
-FGF9 (causes tubes from mesonephric duct to penetrate gonadal ridge, differentiation testes)
-SF1/NR5A1 (differentiation sertoli and leydig cells)
what effect does testosterone have on wolffian ducts?
elongate to form epididymis, seminal vesicles, vas deferens
Mullerian/paramesonephric ducts
- WNT4 protein (signaling factor for ovary, inhibited by SOX9)
- DHH gene (nuclear hormone receptor, upregualted WNT4, downregulated SOX9)
- RSPO1 gene (coactivator of WNT path)
what effect does estrogen have on mullein ducts?
female structures
forms uterus, cervix, broad ligament, fallopian, upper 1/3 of vagina
androgen exposure for males results in what?
penis
scrotum
location of urethral opening
estrogen exposure for females results what?
clitoris
labia majora/minora
lower 2/3 of vagina
when does external genitalia develop?
at 3 weeks
from mesenchymal cells
form genital tubercle, genital swelling
what tests are ordered for disorders of sexual differentiation
first day of life FISH (sex chromosomes) karyotype (chromosome microarray) hormone studies ultrasound surgical consult with urology
Androgen insensitivity syndrome (AIS)
46 XY (genetically male) X-linked AR abnormality of androgen receptor (doesn't recognize/respond) phenotypes range from mild to full reversal of sexualization
5-alpha reductase deficiency
46 XY
mutation means body can’t convert testosterone to dihydrotestosterone
phenotype=undervirilized male with increased virilization at puberty
SRY Gene disorders
46 XY, 46 XX
Y linked gene
-deletion/absence of gene=phenotypically normal female
-ectopic presence of SRY gene in 46XX is a phenotypically normal male
-mutations in 46 XY= decreased/absent production of anti mullein hormone
Denys-Drash and Frasier Syndrome
Sex reversal w/ 46XY
mutations in WT1 gene
different chronic kidney diseases
increased risk wilms tumor
congenital adrenal hyperplasia
ambiguous genitalia 46XX
21-hydroxylase deficiency
salt wasting
