Lecture5,6

Cancer Genetics, Immunogenetics, mapping of human genomesSucheta Tripathy, IICB, 15th Dec 2012

Mutation and diseaseMany of the diseases occur because of

mutation4000 diseases have altered gene.

Heart disease Cancer Auto immune disorders Diabetes

http://www.cancer.gov/cancertopics/understandingcancer/genetesting/GENETEST.PDF

Cancer GeneticsRB1 mutation leads to Retinoblastoma.BRCA1 mutation is linked with breast cancer.

The Cancer Genome AtlasProject to catalogue all mutations in cancer

(2005).GlioblastomaOvarian cancerLung cancer

Gene Expression ProfilingCopy number variationSNP GenotypingGenome wide DNA methylationMicroRNAExome sequencing

ImmunogeneticsGenetic link leading to Immune related dis-

orders.Father of Immuno Genetics is Edward Jenner.

In year 1796 predicted human smallpox can be treated with cowpox.

Multiple SclerosisType-1 Diabetes

Rheumatoid arthritis.

Ref: http://www.idi.harvard.edu/uploads/investigators/Immunogenetics-coi.pdf

IMGT

IMGT

Human Genome Project

In October 1990 Human

Genome project started

First Publication in 2000

Finished paper in 2003

NHGRI Solicited

pilot proposal

for ENCODE

First Report on Encode

Published in 2007

RFAs were sought for

full ENCODE

ENCODE published

2012

GWAS -90% lies outside coding

2005

Genome MappingWhat does it mean?

Mapping multiple variation of the same gene.

HapMap Project:

Mapping Haplotype of human genome

Genetic variants affecting health

Disease and

response to drugs

Environmental

Effects

• To study the effect of environment and their effects on diseases.

• 99.5% DNA are similar.• 269 individuals genotype.• One million SNPs genotyped– Rose to 10 million including

polymorphic sites.

HapMap Project

http://en.wikipedia.org/wiki/International_HapMap_Project

• 95% of the genome is “junk”.– 2.94% of the genome is coding

• cis regulatory elements occur within a limited genome distance.

• Most of the genome is transposable elements that are of obscure origin are dying.

• Transcribed elements are most often translated than not.

What we knew

1000 genomes project

http://en.wikipedia.org/wiki/1000_Genomes_Project

Copy Number Variation

SNPs

Indels

Yoruba in Ibadan, Nigeria; Japanese in Tokyo; Chinese in Beijing; Utah residents with ancestry from northern and western Europe; Luhya in Webuye, Kenya; Maasai in Kinyawa, Kenya; Toscani in Italy; Peruvians in Perú; Gujarati Indians in Houston; Chinese in metropolitan Denver; people of Mexican ancestry in Los Angeles

HapMap ProjectSNPs occurring at least 1% of the population.

If a SNP in one site is known, then the SNP in the nearest site can be identified.

Referencehttp://

www.nature.com/ejhg/journal/v21/n1/full/ejhg201169a.html

http://nar.oxfordjournals.org/content/34/suppl_1/D781.full