Inheritance Flashcards
Features of autosomal dominant inheritance
Affected people in each generation
Males and females
All forms of transmission incl male to male
Risk of inheritance in autosomal dominant
50%
Variable penetrance (likelihood disease manigest if gene change present)
Autosomal recessive inheritance features
Cant always follow disease through pedigree
Males and females affected
Risk of inheriting recessive disease if parents are carriers
25% if both parents carriers
50% - carrier but inaffected
25% chance not carrier or affected
Children of affected parent risk of carrying disease
100% - all children of affected individual will be carriers
Risk of siblings of affected individual being a carrier
2/3
Why do X linked conditions affect men
Women have two X chromosomes - other allele makes up for it
Clues in x linked recessive inheritance
More than one generation affected
Only males effected
No male to male tranmission - males dont pass chromosome to their son
Risk of disease inheritacne X linked recessive
25% risk affected male in each pregnancy
Risk of unaffected male per pregnancy X linked
25%
Risk of unaffected male each pregnancy X linked
25%
Chances of non carrier female without condition
25% chance
Risk of carrier daughters and sons
50% risk
What is important to ask in a family history of genetics
Relationship breakdonw - divorce/estrangement
Adoption/other biological relationships/non paternity
Causes of daeth other than natural eg accidental, suicide, drug/alcohol related
Bereavment incl miscarrigae and abortion
Consanguinity - incest
What is a genomic test types
Analysis of DNA
Diagnostic - Test which seeks to confirm a clinical diagnsois
Predictive - test offered to relatives of someone confirmed genetic cancer
What is SNV vs CNV
SNV - variation in a single nucleotide (A or G)
Ins/del of a series of nuelotides (base pairs)
CNV - large scale duplication or deletion
What stain used to view chromosomes and how appear
Giemsa
Striped G banding
Allows chromosomes to be distinguished from each pther
What is karyotype analysis used for
Detecting whole chromosome changes eg trisomy, monosomy and translocation
Starting to be replaced w CGH
What is FISH used for
Microdeletion or microdulpication detection
Specific situations and cancer diagnoses
What is (aCGH
Array comparative genome hybridisation
How is aCGH done
DNA in solution broken into fragments labelled w fluroresent dye
DNA from control in equal quantities - diff colour dye
Hybridise - stick to matching sequence DNA
What happens if patient missing DNA fragment in aCGH
If missing fragment -> more control DNA bind to corresponding detector molecule -> NORMAL colour on UV ligtj
What colour signal given if patient and control sample the same
Fusion colour signal
What does a patient colour signal mean aCGH
Duplication of fragment
What can and cant aCGH detect
Trisomy, CNVs, microdeletions and smaller ins/dels
Wont detect single nucloetide changes and cannot detect balanced translocations
What is the key feature of next generation sequencing
Read and re-read fragments of DNA in solutino very quickly and reliably
Allows check whole genome or panel, real or virtual controls, generate significant results without being asked specifically
What is an exome
1% of genoma - 18,000 genes
What is sensitivity of a genomic test determined by
Technical - how good is lab technique
Gene coverage - can we test all relevant parts of genes ass w particular phenotype
Phenocopy - existence of non genetic conditions mimicing a genetic diorder
What is specificity of genomic test
Variation in single gene can be caused by other diseases
eg Huntingtons disease ONYL caused by CAG repeat of HTT gene
whereas familial HCM - mutation in number of different genes - only 70% diagnostic sensitivitt
Same genes may also cause different disease eg LV hypertrophy
Problems with genomic testing sensitivity and speciicity
Variable expressivity and peneterance - whether all genes that cause disease known or tested for and which disease genes can cause
