Lecture 4+5: Online Resources

Question 1

1000 Genomes Project (1KGP) goal

Answer 1

-create catalogue of human genetic variation by sequencing genomes of at least 1000 ppl from various ethnic groups

Question 2

1KGP experiment

Answer 2

-2,504 healthy individuals from 26 populations
-short-read DNA sequencing

Question 3

1KGP findings

Answer 3

-ppl from dif populations carry dif profiles of rare and common variants
-low-freq variants show substantial geographic differentiation
-on average, each person has 250-300 loss of function variants!!! in annotated (protein coding) genes and 50-100 variants previously implicated in inherited disorders

Question 4

1KGP significance (no star)

Answer 4

-resource of human genetic diversity
-identify many rare genetic variants
-help understand genetic basisi of diseases
-jumpstarted PGx

Question 5

1KGP in Ensembl

Answer 5

-Ensembl database stores areas of genome that differs and disease and phenotype info
-SNPs, indels, NVs

Question 6

HGVS nomenclature (no star)

Answer 6

-must include a reference sequence

Question 7

Other databases

Answer 7

-NCBI (NIH)
-gnomAD
-OMIM
-MARRVEL
-NIH GDC portal (Cancer)
-project mine (ALS)
-AD knowledge portal (AD)
-SFARI gene (Autism)

Question 8

First place to check

Answer 8

-PHARMGKB

Question 9

PHARMGKB info

Answer 9

-prescribing info
-clinical guideline annotation
-see if change of meds is needed after genetic test

Question 10

Your 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 10

-More info is needed
-do NOT treat it like a known mutation