Lecture 4: Genomics and Health

Question 1

What is the traditional route to gene discovery?

Answer 1

Determine mode of inheritance 
Recombination mapping using markers
Haplotype analysis of recombinants 
Rapid screening of candidate genes for mutations 
Confirm by sanger sequencing

Question 2

What is the state of art route to gene discovery?

Answer 2

Whole exome next generation sequencing
Filter polymorphism to give list of candidate genes
Confirm by sanger sequencing

Question 3

Describe exon capture

Answer 3

Synthesise chip using RT-PCR
Use cDNA library to get target gene. Fragment this sample
Apply the sample to the chip
Wash off unbound sample and this goes to waste
Elute captured material which is sequenced

Question 4

What is the criteria for filtering?

Answer 4

Mutation likely to cause a change in gene expression or protein structure
Mutation not commonly found in SNP databases or control genome sequences
Alleles in affected individuals correspond to mode of inheritance
Same gene mutated in affected unrelated individuals
No unaffected individuals with putative disease causing genotype

Question 5

What are features of de novo mutated Cantú syndrome

Answer 5

Congenital hypertrichosis (excess hair)
Distinct facial features
Osteochondrodysplasia
Cardiac defects
Dominant inheritance

Question 6

Where is the mutation in cantú syndrome?

Answer 6

ABCC9 gene (ATP- dependent K+ transporter)

Question 7

What is SNP?

Answer 7

Single nucleotide polymorphism