Lectures 4-5: Online Resources

Question 1

1000 Genomes project (1KGP)

Answer 1

Goal; To create a detailed catalogue of human genetic variation by sequencing the genomes of at least 1,000 various ethnic groups

Experiment: 2,504 health individuals from 26 human populations

short-read DNA sequencing

Question 2

What was learned from 1KGP

Answer 2

Different populations carry different profiles of rare and common disease variants

Question 3

Major findings 1GKP

Answer 3

Low-frequency variants show substantial geographic differentiation

On average, each person carries 250-300 loss of function variants in annotated genes and 50-100 variants previously implicated in inherited disorders

Question 4

1GKP data in Ensembl

Answer 4

The Ensembl Variation database stores areas of the genome that differ between individual genomes (“variants”) and, where available, associated disease and phenotype information

The are different types of variants:

-SNPs
-Short nucleotide insertions/deletions
-Longer variants classified as structural variants (including CNVs)

Question 5

HGVS nomenclature

Answer 5

In order to have a unique description, you most include a reference sequence

Question 6

Q: You order a DNA test for your patient to sequence all possible alleles in all exons of CYP2C19 genes. After sequencing, no known mutant allele was identified (this is why it was called as 1/1. However, a novel mutation (heterozygous) in CYP2C19 exon 3 was identified. This allele has never been described in the literature. What would you do with this finding?

Answer 6

More information is needed to evaluate its clinical consequence