Human Genome (Mapping And Diagnosis)

Question 1

How many genes do humans have?

Answer 1

30,000

Question 2

% of genome that is genes? Coding %?

Answer 2

30% genes, 10% coding

Question 3

How do you identify a candidate gene responsible for single gene defect?

Answer 3

1. If PROTEIN SEQUENCE known —> generate cDNA, generate probe, screen DNA library, isolate gene
2. If you know a member of a GENE FAMILY that causes a certain disease, then similar ones could be caused by other members of that family (e.g. fibrillin 1 —> Marfan; fibrillin 2 —> congenital contractural arachnodactyly)
3. If known gene ANIMAL HOMOLOGUE causes a similar phenotype in an animal, then human homologue might cause human phenotype
4. If some cases are shown to be caused by one defective gene product of a METABOLIC PATHWAY but not other cases, the other cases might be caused by gene products at other points along the same metabolic pathway
5. If it shows ANTICIPATION, maybe unstable expanding DNA repeat
6. If it shows CYTOGENETIC CLUES

Question 4

What does linkage mean?

Answer 4

Genes that are linked have very close gene loci such that the probability of recombination is small and the probability of co-inheritance is large

Question 5

What is a polymorphic marker, and why are they useful?

Answer 5

One that is frequently heterozygous in a population, such that you can distinguish two copies of a gene that an individual inherits

Question 6

What are VNTRs?

Answer 6

Variable number tandem repeats

Changes in the number of repeated DNA sequences arranged in tandem arrays

(E.g. 3-alleles vs 5-alleles vs 2-alleles)

Question 7

What are microsatellites/STRs/SSRs?

Answer 7

Class of VNTR with 1-6 bp repeats

STR = short tandem repeat; SSR = simple sequence repeat

Question 8

What are SNPs?

Answer 8

Single nucleotide polymorphism

Single base insertion/deletion/substition

Question 9

What is linkage analysis?

Answer 9

Mapping a trait on the basis of its tendency to be co-inherited with polymorphic markers.

So for e.g. there is a polymorphic marker very near the huntingtin gene so if you inherit the same polymorphic marker as the family member with a huntingtin gene mutation, then you have also inherited the huntingtin gene

Question 10

Check out linkage slide

Answer 10

P39 of Lisa Walker lecture slides

Question 11

Gorlin syndrome?

Answer 11

Predisposition to basal cell carcinoma

Autosomal dominant

Question 12

How do affected sibling pairs help in doing linkage analysis on polygenic diseases?

Answer 12

Look at number of alleles that siblings share across the genome

Then do it for lots of siblings

Find a broad region of linkage, list the genes within the linkage, then possibly identify the causal polymorphism

Question 13

What is a genome wide association study, and what type of genetic disease does it look for?

Answer 13

Isolate candidate genes that may confer susceptibility to condition - their individual effects are small, so it is cumulative/additive

Looks for polygenic diseases

Question 14

What is the Oxford Biobank?

Answer 14

Big GWAS

Aims to recruit 0.5m people aged 40-69 across Britain

Take blood samples and track long term health

Question 15

What is used to map single gene disorders and how does this compare with polygenic disorders?

Answer 15

Single = whole genome sequencing
Polygenic = genome wide association studies

Question 16

Which parental chromosome 15 do you NEED to NOT get Prader-Willi syndrome?

Answer 16

Father, therefore 2 copies of mother’s chromosome leads to Prader-Willi

Question 17

Which parental chromosome 15 do you NEED to NOT get Angelman’s syndrome?

Answer 17

Mother, so 2 copies of father’s chromosome leads to Angelman’s

Question 18

Miscarriage risk after amniocentesis?

Answer 18

0.5-1%