Genetics Flashcards
How can placental tissue be obtained for genetic testing?
Chorionic villus biopsy from 11.5 weeks gestation
Testing with FISH or PCR for chromosome abnormality
How can skin/urine cells of a foetus be obtained for genetic testing?
Amniocentesis from 16 weeks gestation
How can blood of a foetus be obtained for genetic testing?
Foetal blood sampling from 18 weeks gestation
How can foetal DNA be obtained for genetic testing?
Maternal serum from 8 weeks gestation
Rank chorionic villus biopsy, amniocentesis, foetal blood sampling and maternal serum in order of greatest to smallest risk of miscarriage
Chorionic villus biopsy
Foetal blood sampling
Amniocentesis
Maternal serum (no risk)
Rank chorionic villus biopsy, amniocentesis, foetal blood sampling and maternal serum in order of most viable to least viable tissue
Chorionic villus biopsy
Foetal blood sampling
Maternal serum
Amniocentesis
What is confined placental mosaicism? Which method of genetic testing is it most associated with?
Discrepancy between chromosomal makeup of placental cells and cells in the baby
Chorionic villus biopsy
List the indications for chromosomal analysis in pregnancy
Raised maternal age
Increased risk on screening: nuchal thickness, serum, DNA
Abnormality on ultrasound
Known parental abnormality
What does array CGH analyse?
Changes in the number of copies of a particular gene in a diseased state
Basically looks at chromosome makeup
List the 4 main genetic tests used for chromosome analysis and state whether these tests assess the whole genome or are targeted
Array CGH (whole genome)
Standard karyotype (whole genome)
FISH (targeted)
QF-PCR (targeted)
What is the earliest stage of pregnancy where nuchal thickness can be assessed via ultrasound?
12 weeks
List indications for obtaining free fetal DNA
Antenatal screening for down’s syndrome
Fetal sexing for X-linked disorders
Monogenic disorders
Distinguish a mutation from a polymorphism
Genetic change that causes disease
Genetic variation that is not disease-causing
List the most common types of chromosomal abnormalities
Aneuploidy (abnormal no. of chromosomes in a cell)
Rearrangements (translocations, inversions)
Deletions/ duplications
List the main types of chromosomal translocations
Robertsonian (two acrocentric chromosomes end-end)
Balanced (all chromosome material present)
Unbalanced (extra or missing chromosome material)
Which type of chromosomal translocation is the most common reproductive risk?
Unbalanced chromosomal translocation
Large segments of unbalanced chromosomal translocation causes…
Miscarriage
Small segments of unbalanced chromosomal translocation causes…
Dysmorphic delayed child
What does pre-implantation genetic diagnosis (PGD) involve?
Perform a genetic test on an embryo before re-implanting it with “correct” genotype, using IVF
What method is used to implant genetic info in PGD?
Intra-cytoplasmic sperm injection (ICSI)
How old is the embryo when it is biopsied in PGD?
3 days
List types of DNA analysis commonly used and their relative indication in pregnancy
aCGH for deletions/duplications in small sequences
Chromosome analysis for balanced rearrangements
NGS for large sequences
Non-invasive prenatal testing for large sequences
What type of mutational change would produce an abnormal or absent protein?
Splice consensus altered
What type of mutational change would make a short or absent protein?
Base change makes new stop
What type of mutational change would make a different or non-functioning protein?
Base change alters amino acid sequence
What is the main disadvantage of NGS in pre-natal testing?
It detects lots of polymorphisms
When can fetal anomalies be identified during pregnancy on US scan?
Booking scan (10-12 weeks) Detailed scan (20 weeks)
What is the pattern of inheritance for Duchenne muscular dystrophy?
X-linked recessive
Gene that can carry a DMD-causing mutation is on the X chromosome which passes from mother to son
What is the risk of a child being affected by DMD?
1 in 4
1 in 2 if you know the child is male
What is the risk of a child being affected by an autosomal dominant condition?
1 in 2 risk if parent is affected
What is the risk of a child being affected by an autosomal recessive condition?
1 in 4 risk of affected child if parents are carriers
What factors influence risk estimation of a child?
Family history Obstetric history Maternal history Scan findings Genetic tests
What is the best genetic management if DNA testing in pregnancy indicates risk of inheritance?
Non-invasive fetal sexing
Chorionic villus biopsy if male
List indications for consideration of PGD in pregnancy
Parental chromosomal abnormality (robertsonian translocation, reciprocal translocation)
X-linked disorders (reimplantation of female embryo)
Other single gene disorders (spinal muscular atrophy, cystic fibrosis, huntingdon’s disease)
What is a Robertsonian translocation?
Chromosomes break at their centromeres and the long arms fuse to form a single, large chromosome with a single centromere
What is a reciprocal translocation?
Chromosome abnormality caused by rearrangement of parts between non-homologous chromosomes
