Genetics Flashcards
Examples of Autosomal dominant disease?
Adult polycystic kidney disease BRCA 1 and 2, MEN, Lynch, VHL Connective tissue disease e.g. Achondroplasia, Ehlers Danlos, Osteogenesis imperfecta FAP Familial hypercholesterolaemia Familial retinoblastoma Fragile X Hereditary Spherocytosis Huntington's Marfan's Myotonic dystrophy Neurofibromatosis Type 1 PCKD VWD
Examples of Autosomal recessive disease?
Alpha anti-trysan CF Factor V Leiden Friedrich’s ataxia Haemachromatosis PKU Sickle cell Thalassaemia Tay sacks
X-linked recessive conditions?
Duchenne
Haemophilia A
AD inheritance pattern?
Each child 50% risk No skipped generations Male to male transmission May have incomplete penetrance Occurs in each generation - if skipped may be due to non penetrance
AR pattern of inheritance?
Need one from each parent
Equally transmitted by males and females
Males are infertile
If a person is a carrier (heterozygote) of an AR allele, they always have a 1/2 (50%) chance of passing on allele
1/4 chance of next child
If one child affected, other children have 2/3 chance
chance of unaffected child having gene is 2/3
Consanguinity common, especially for rare disorder)
X linked dominant inheritance.
Pattern of inheritance?
Examples
Hemizygous males have full phenotype (severely affected, usually lethal in pregnancy or neonatal)
Heterozygous females are typically unaffected or only mildly affected
NO male to male transmission
examples:
Rett syndrome
Mitochondrial pattern of inheritance?
Examples
Females will pass on to all children.
Examples:
Leber Hereditary optic neuropathy (LHON)
MELAS (myopathy, encephalopathy, ALctic acidosis, Stroke like episodes)
Myoclonic epilepsy with Ragged Red Fibres (MERRF)
Neuropthy, Ataxia and Retinitis Pigementaosa (NARP)
Examples of triple repeat disorders?
Fragile X
Huntington’s
Myotonic dystrophy
What is Mosaicism vs. chimerism?
A mosaic individual has 2 or more genetically different cell lines derived from the same zygote.
A chimeric individual has 2 or more genetically different cell lines derived from 2 or more zygotes.
What is genome imprinting?
Epigenetic marking based on its parental origin that results in mono allelic expression
Imprinting = switched off
Female pt with Fragile X syndrome shown to carry a CGG repeat size of 180 (witin premutation range). What are the risks to her of transmitting Fragile X syndrome to her offspring?
50% chance of passing on the pre-mutation allele which could expand into full mutation as she is a female transmitting parent. AD inheritance unstable on maternal transmission -> anticipation
What level of repeat is required for triple repeat expansion for normal, intermediate, permutation and full mutation?
Normal 11-44 repeats
Intermediate 45-58 repeats
Premutaiton 59-200 repeats
Full mutation > 200
What is chromosomal microarrays?
A method to assess thousands of DNA sequences to detect sub-microscopic chromosomal imbalances (gains or losses).
Will not detect a balanced X-autosome reciprocal translocation
What are the features of mitochondrial inheritance?
Maternal, will pass on to all her children
High mutation rate
Multiple copies
Variable expressivity is common
X-linked dominant female carriers will show a phenotype. T/F
True, milder than males
X-linked recessive shows no phenotype
What is the inheritance of BRCA mutation?
AD
If concerns of BRCA mutation, test affected family member for mutation
Point mutation is a type fo DNA mutation? What are the 4 Types?
A change in a single base pair.
Missense = spelling mistake e.g. THE BIG RAD DOG -> gain of function
Nonsense = stop codon e.g. THE BIG RED -> loss of fucntion
Frameshift deletion = deletion e.g. THE BRE DDO G -> loss of function
Frameshift insertion = insertion e.g. THE BIG RED ZDO G -> loss of function
what is a splice site mutation?
A change that results in altered RNA sequence.
usually due to point mutations but can be insertions or deletions.
i.e. exon spliced out or intron left in. Introns are meant to be spliced out.
An intron is a region of a gene that does not code for a protein
What is linkage analysis?
A test to look for patterns of DNA markers near gene of interest that segregate with disease. Requires DNA analysis of multiple family members
What is the recombination fraction?
The freq with which a single chromosome cross over will take place between 2 genes during meiosis i.e. the chance they will break up
What would a deletion in an exon cause?
Leads to deletion of dystrophin protein resulting in Duchennes muscular dystrophy
