Obstetric Genetics Flashcards
Inheritance patterns
autosomal dominant
autosomal recessive
X-linked recessive
Autosomal dominant
heterzygotes with one copy of the abnormal gene are affected
Autosomal recessive
homozygotes with two copies of the abnormal gene are affected
X-linked recessive
males with one copy of the abnormal gene on the X chromosome are affected
carrier females unaffected
all men who inherit mutation are affected
Example of X-linked recessive
Duchenne Muscular Dystrophy
most common, 3-5 years, learning difficulties, Gower sign
Also: Haemophilia
Example of autosomal recessive
CF
progressive lung disease, affects lungs, pancreas, male infertility
Also: beta-thalassaemia
What information is needed to calculate carrier risk?
risk figure for both parents being a carrier
How to calculate risk for offspring
parent CR x parent CR x probability child will inherit 2 copies of mutation
How to calculate carrier rate for recessive condition
Hardy-Weinberg principle: can calculate once incidence is known
What is needed for H-W principle to work?
gene frequency in equilibrium
large, randomly mating population
no outside influences
2 alleles for autosomal condition
Equation
if autosomal recessive condition
p2 + q2 + 2pq = 1
AA aa Aa
p2 = homo unaffected 2pq = carriers q2 = affected
Factors affecting H-W principle
assortative mating, tendency to choose similar mate consanguinity - rs with close relatives selection founder effect migration (gene flow)
Routine prenatal screening
ultrasound - date baby, dating, single/twins
NT scan - thickness of neck in US, detect anomalies such as Down’s, major congenital heart disease
ultrasound - more detail, cleft lip
Targeted tests
family history
abnormalities in pregnancy
Non-invasive tests
US, fetal MRI, molecular testing on fetal cells/DNA in mother’s blood
Invasive tests
chorionic villus sampling - placenta
amniocentesis - amniotic fluid
cordocentesis - fetal blood
fetal tissue biopsy
What is preimplantation genetic diagnosis?
and process?
testing embryos produced by IVF for inherited disorders
- stimulate ovulation
- oocyte retrieval
- fertilisation and culture
- blastocyst biopsy
What is the universal screening?
blood spot - day 7
test for: phenylketonuria, CF, sickle cells
Polygenic inheritance
inheritance caused by multiple genes with small additive effects
Multifactorial
condition caused by multiple genes
Liability to be affected
environment + genetic predisposition
liability - threshold model is a curve to show affected
Recurrence risks
relatives affected
greatest for closest relatives
increased risk is great severity in affected relatives
more than one risk
increased risk if gender with lower risk is affected
