Nucleotide variation in the human genome

Transcription

1 Nucleotide variation in the human genome Elena Salmerón Quesada Genomics 13/12/2017

2 HUMAN GENETIC VARIATION 84.7 MILLION SINGLE NUCLEOTIDE POLYMORPHISMS (SNPs) 3.6 MILLION INDELS STRUCTURAL VARIANTS

3 millions SNPs IN THE HUMAN GENOME 84.7 MILLION SNPs Single base variations between genomes within species Common variants Low frequency variants Rare variants >5% 0.5 5% <0.5% -High frequency -Common disease by GWAS -Very low frequency -Rare and common disease Characteristic SNPs - Populations

4 SNPs LOCATION Coding region Non-coding region Non-synonymous Synonymous -Gene splicing - No effect -Transcription factor binding

5 HAPLOTYPE Haplotype: specific set of alleles observed on a chromosome

6 PROJECTS STUDYING HUMAN GENETIC VARIATION AIM: Create a haplotype map of the human genome - Focus on >1% frequency SNPs Individuals from 4 populations Million SNPs AIM: A more complete characterization of human genetic variation - Discover all common Human variation Individuals individuals from 26 populations Million SNPs

7 SNP GENOTYPING Illumina: Infinium genotyping arrays ~5 million selected SNPs SNP genotyping via direct hybridization ~ 1000 samples Silica beads

8 APPLICATIONS Diagnostic Drug efficacy and adverse drug reactions Predisposition to disease Forensics Follow ethnic migrations Animal and plants breeding programs

9 APPLICATION: DISEASE 60 prostate cancer risk SNPs common in about 5% of the population Susceptibility but not aggressiveness A rare 8q24 single nucleotide polymorphism (SNP) predisposes American men to more aggressive disease 3 SNPs significant association with aggressive prostate cancer in African-American men DIAGNOSTIC + TREATMENT DESICIONS

10 APPLICATION: DRUGS rs SNP in the BCHE gene. Succinylcholine (anesthetic) depends on BChE hydrolysis for recovery. Prolonged muscle paralysis + potentially lethal effects AVOID ADVERSE DRUG RESPONSE butyrylcholinesterase (BuChE) enzyme affected

11 APPLICATION: FORENSIC SCIENCE PREDICTION Pigmentation (Skin, eye, hair ) Height Facial morphology Geographic ancestry 1 MILLION SNPs REAL Phenotypic appearance PERSONAL IDENTIFICATION Modeling Suspects' Faces Using DNA From Crime Scenes

12 CONCLUSIONS SNPs: Relevant to understand human variation Relatively easy to genotype Wide range of useful applications

13 LITERATURE 1000 GenomesProject Consortium; Auton, A., Brooks, L.D., Durbin, R.M., Garrison, E.P., Kang, H.M., Korbel, J.O., Marchini, J.L., McCarthy, S., McVean, G.A. & Abecasis, G.R. (2015)A global reference for human genetic variation. Nature :68-74 Grin B1, Loeb S, Roehl K, Cooper PR, Catalona WJ, Helfand BT. A rare 8q24 single nucleotide polymorphism (SNP) predisposes North American men to prostate cancer and possibly more aggressive disease. BJUint /bju Lou, C., Cong, B., Li, S., Fu, L., Zhang, X., Feng, T., Su, S., Ma, C., Yu, F., Ye, J. and Pei, L. (2011), A SNaPshot assay for genotyping 44 individual identification single nucleotide polymorphisms. ELECTROPHORESIS, 32: doi: /elps Garcia DF, Oliveira TG, Molfetta GA, et al. Biochemical and genetic analysis of butyrylcholinesterase (BChE) in a family, due to prolonged neuromuscular blockade after the use of succinylcholine. Genetics and Molecular Biology. 2011;34(1): doi: /s International HapMapProject: genomes project:

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