Genetics Flashcards
What is a polymorphism?
The occurrence of two or more genetically determined phenotypes in a certain population
NB - this is benign, in contrast to a mutation
What is a variant of unknown significance?
When the lab cannot determine whether a gene change is deleterious (harmful) or a benign polymorphism
What is a predictive test?
A test done in a newborn to detect genetic characteristics that have been proven to exist in the parent, but have not yet altered the child phenotypically
What is cytogenetics?
The field of looking at ones chromosomes using:
- Karyotype
- FISH
- array cGH
What is sequencing?
Molecular testing to look at anything from a single gene base to a whole exam
Describe autosomal dominant inheritance
If one parent is affected, there is a 50% chance that the child will be
Describe autosomal recessive inheritance
If one parent is affected, there is a 25% chance that the child will be
Describe mitochondrial inheritance
The trait can only be inherited from the mother, as it lies in the mitochondria
What is penetrance?
The proportion of individuals with a genetic mutation that manifest the disease
What is genetic counselling?
The process by which patients or relatives at risk of a genetic disorder are advised of the consequences of the disorder, the probability of transmitting it and ways in which it can be prevented
How are the following genetic conditions diagnosed:
a) NF1
b) Marfans
c) early onset epilepsy
a) clinical
b) specific gene test
c) gene panel as there is no specific causative gene
What is a triple repeat disorder? Give an example?
Dominant mutation caused by an increased number of copies of a tandemly repeated trinucleotide
eg. Huntingtons - increased CAG repeat over 40 repeats
What is anticipation?
Give 2 conditions which show this pattern
When a genetic condition becomes more severe in successive generations
Huntingtons, myotonic dystrophy
What is age related penetrance?
Give 3 conditions which show this pattern
When the frequency of disease changes at different ages
Huntingtons, myotonic dystrophy, fragile X
What is genetic heterogeneity?
Give a condition which shows this pattern
When a clinical phenotype can be caused by mutations in any one of a number of different genes
Long QT syndrome
What is the genetics of Marfans syndrome?
FBN1 mutation leading to skeletal, ocular, cardiac complications
What is variable expression?
Give a condition which shows this pattern
When the phenotype differs amongst individuals carrying the same genotype
Marfans
What is the genetics and features of NF1?
Mutation in NF1 gene, causing cafe au last spots, hearing difficulties and bone deformities.
Shows 100% penetrance and variable expression
What is the genetics and features of tuberous sclerosis?
Mutation in TSC1/2 genes, causing skin changes, renal lesions, cerebral lesions and seizures
Shows 100% penetrance and variable expression
How is the ApoE allele involved in alzhemiers?
Different forms of the allele can affect risk of disease.
E2 - protective
E3 - normal
E4 - risk allele
What syndrome causes isolated cleft lip and palate?
Van de Woude syndrome
autosomal dominent, variable expression
What syndrome causes cleft lip, cardiac problems and polydactyly?
Patau’s syndrome
trisomy 13, usually incompatible with life
What syndrome will a de novo mutation in CHD7 cause?
CHARGE syndrome Coloboma (hole in eye) Heart defects Atresia of nasal passage Retardation of growth Genital and urinary tract abnormalities Ear abnormalities/hearing loss
Describe the features of fetal valproate syndrome
NB - specify what facial features
Cardiac defects, cleft lip, genitourinary abnormalities, developmental problems
Face - tall forehead, medial eyebrow deficiency, flat nasal bridge, shallow flirt, long upper lip
Give 5 examples of teratogens
Infection (CMV/rubella) Tobacco Thalidomide Radiation Alcohol
What is aneuploidy?
An abnormal number of chromosomes (i.e.. not 46)
Give an example of a trisomy
Downs syndrome (21)
Pataus (13)
Edwards (18)
Give an example of a monosomy
THERE IS ONLY ONE VIABLE MONOSOMY - 45X (Turners Syndrome)
What is a balanced structural chromosomal abnormality?
When breakage of chromosome segments results in no loss or gain of genetic material 3 Types: Reciprocal translocation Inversion Insertion
These can usually be seen on a karyotype
What is reciprocal translocation?
A balanced chromosomal abnormality involving exchange of genetic material from two non homologous chromosomes
What is inversion?
A balanced chromosomal abnormality when a segment is reversed end to end within the chromosome
What is insertion?
A balanced chromosomal abnormality in which a portion of one chromosome is deleted from its normal place and inserted into another chromosome
How can a balanced chromosomal abnormality be detected?
Look at karyotype
What is an unbalanced structural chromosomal abnormality?
When breakage of chromosomal segments results in addition or subtraction of genetic material
2 types:
Deletion (eg. Di George Syndrome)
Duplication (extra genetic material)
How can an unbalanced structural chromosomal abnormality be detected?
Look at FISH or arrayCGH
What is Robertsonian Translocation?
Breakage of two acrocentric chromosomes (ie. one long arm one short arm)
Translocation then leads to one long large chromosome with most of the genetic material, and one small one which is usually lost within a few cell divisions.
Which chromosomes can undergo robertsonian translocation?
13, 14, 15, 21, 22
How does microarray work?
DNA based technique that examines the whole genome for gains/losses of genetic material by looking at changes in the COPY NUMBER VARIANTS (repeats)