Human Pedigrees Flashcards
Name the 6 types of Mendelian inheritance
Autosomal dominant, Autosomal recessive, X linked dominant, X linked recessive, Y linked Mitochondrial inheritance
Name a mutation which causes achondroplasia
Single base mutation in the fibroblast growth receptor 3 on chromosome 4 at 1138
What is autosomal recessive
On non sex chromosomes, need both copies of the allele to have the condition. Not expressed in every generation more in consanguineous marriages
What is an example of a autosomal recessive condition
Cystic fibrosis, freq 1/2000 causes infertility in males and low fertility in females, causes a build up of thick sticky mucus in the lungs and intestines
Is a mutation in the cystic fibrosis transmembrane conductance regulator gene encoding for membrane bound chlorine channels
What is X-linked Dominant?
Seen in every generation women more likely to suffer than men
Example of an X-linked dominant condition
Hypophosphatemia with vitamin D resistant rickets (HPDR1)
Freq 1/20000
Causes growth retardation, childhood rickets, reduced serum phosphate female hetrozygotes phenotype variable lyonization
What is X-linked recessive
Mainly males effected unless have two X chromosomes with the allele
Example of a X-linked recessive condition
Duchenne muscular dystrophy (DMD) mainly affects males, severe progressive proximal muscle weakness die at 20 years
Complications of X-linked inheritance
Male lethality if passed onto from the mother so may die in Utero half is passed on to their daughters
Eg incontinentia pigmenti
Name 5 repeat expansion diseases
Fragile X syndrome SBMA Huntingtons disease Friedreich ataxia Myotonic dystrophy 1
What causes myotonic dystrophy (AD)?
An epansion of the triplet repeat CTG in the 3’ untranslated region of the gene on 19q.
No of repeats increases through generations thus increasing severity
What is a polymorphic trait?
Proteins which have little variation such as blood groups and antigens
What is genetic mapping used for?
Measuring the recombination between genes that cause a disease/trait and polymorphisms within the genome
How many SNPs can be expected per generation?
6-60 mutations
What are minisatellites used for?
DNA fingerprinting
How can SNPs be analysed
Restriction fragment length polymorphisms
What can be used to analyse STRs?
PCR
What is the maximum recombination frequency?
50%
How do you calculate RF
Recombinants/total progeny
What does one RF unit represent?
1%=1cM (centi Morgan) =1x10^6 np
How do you calculate a lodscore?
[(1-theta)^5 theta^1] / [(1-0.5)^5 0.5^1]
What does the maximal lodscore represent?
The most probable position of the disease locus
What are the 5 Lodscore limitations?
Requires genetic model for mode of inheritance
Errors in data scoring, entry, misdiagnosis
Limitations in families that can be analysed
Not useful if there is locus heterogeneity
Limits in resolution
What is a haplotype?
A particular combination of alleles at closely linked loci that are inherited together in families
What type of disease can use haplotypes to track them?
Ones with locus heterogeneity eg deafness
What is linkage disequilibrium?
Non-random association of alleles at linked loci in a population
4 Factors that influence linkage disequilibrium
Recombination or gene conversion breakdown
Recurrent mutation
Population dynamics eg genetic drift and migration
Natural selection
Define autosomal dominant
Seen in every generation, non sex bias you only need one allele to have the condition, mutations tend to occur in germline cells usually in sperm due to the volumes produced
