Pregnancy and Early Childhood 🗸 Flashcards
silent mutation
mutated codon codes for the same amino acid
triplet expansion
a triplet is repeated
recessive autosomal inheritance is more common in which types of families
consanguineous (same ancestor)
de-novo dominant inheritance
occurs when a de-novo variant in one copy of a gene is sufficient to result in a clinical phenotype
de-novo
from neither parent, a new mutation
Array-CGH
allows you to look for sub-microscopic deletions or duplications of chromosomal material across the whole genome
only detects chromosome imbalance
next generation sequencing (NGS)
finds small sequence changes
Non-invasive prenatal testing (NIPT)
uses free foetal DNA in maternal circulation
currently used for sex determination and trisomy testing
if there is more of chromosome 21, the pregnancy is high risk (99%) of trisomy 21, if not then it is low risk
advantages of NIPT
allows for fewer tests
non-invasive so no risk of miscarriage
disadvantages of NIPT
can give false negatives due to inadequate foetal fraction, only 10% of the DNA comes from the foetus
can give false positives due to confined placental mosaicism or maternal malignancies
Invasive testing
uses aCGH
sample taken from placenta (chorionic villus sampling) or from amniotic fluid (amniocentesis)
what can invasive testing indicate?
when scanning you can see foetal abnormalities like small size, symmetrical growth failure, increased nuchal thickness or structural failures (brain/heart etc)
you can also see if the parent has a balanced chromosomal rearrangement
advantages of invasive testing
higher resolution
technically easier
rapid
disadvantages of invasive testing
also finds polymorphisms (SNPs or CNVs) so may make incidental findings
1/100 risk of miscarriage for invasive tests
termination of pregnancy (TOP)
surgical TOP before 13 weeks, must be induced after that
no time limit on TOP if there is a serious abnormality or health concern of the mother
when would NGS be used on an infants genome?
when the infant presents with a phenotype indicative of a genetic disorder, after other testing has taken place, conformation of sorts
filtering mutations
3 million variants = exclude variants know to be polymorphisms
1000s of variants = keep variants known to affect gene function
100s of variants = does the gene explain the phenotype?
should leave one mutation, which is causative
trio exome sequencing
NGS used to sequence the exome of the mum, dad and kid
used as a first line test for unwell children with a likely monogenic disorder
20-40% diagnostic rate with no environmental cause and up to 70% for a kid with abnormal neurological presentation
pre-implantation testing
perform a genetic test on an embryo before re-implanting one with the ‘correct’ genotype
can be considered in parental chromosome abnormality or single gene conditions
genetic testing in kids
identify phenotype, dysmorphology database and other resources can help
use aCGH to look for chromosomal imbalance
use UGS to look for smaller mutation, requires filtering
