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Detection of positive selection in humane genome

Detection of positive selection in humane genome. Introduction. Introduction. Before and after genome sequencing. Detection Methods. 1.- High proportion of function-altering mutations.

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Detection of positive selection in humane genome

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  1. Detection of positive selection in humane genome

  2. Introduction

  3. Introduction Before and after genome sequencing

  4. DetectionMethods

  5. 1.- High proportion of function-altering mutations Sperm proteamine P1: Protamines are small, arginine-rich, nuclear proteins that replace histones late in the haploid phase of spermatogenesis and are believed essential for sperm head condensation and DNA stabilization

  6. 2.- Reduction in genetic diversity Region with low diversity and excess of rare alleles

  7. 3.- High-frequency derived alleles African populations Thought to be the result of selection for resistance to P.vivax malaria.

  8. 4.- Differences between populations

  9. 5.- Long haplotype

  10. Results • Candidate region characteristics: • Mean length : 815kb • Max length: 3.5Mb • Often contain multiple genes. Mean: 4 Max: 15 • A typical region harbour 400-4000 common SNP (frec >5%) • ¾ SNP database ½ Genotyped HapMap2 ¿Which are the true signatures of positive selection?

  11. They performed a similar analysis on all the 22 candidate regions. 9166 SNPs associated with the long-haplotype signal (Long haplotype) 480 satisfied the two other criteria (Population differences and Derived allele) 41 (0’2% of all SNPs genotyped in the regions) possibly functional on the basis of newly compiled database 41 SNPs: 8 encode non-synonymous changes. SLC24A5 (well kwon) · EDAR PCDH15 · ADAT1 KARS · HERC1 SLC30A9 · BLFZ1 The remaining 33 potentially functional SNPs lie within Conserved transcriptional factors motifs Introns UTRs Other non-coding regions Results • SLC24A5: • 600KB region • 914 genotyped SNPs • Filter application: • 857 SNPs associated with long-haplotype signal • 233 of 867 are high-frequency derived alleles • 12 of which are highly differentiated between populations • 5 of which are common in Europe and rare in Asia and Africa • 1 of these 5 is only one implicated as functional by current knowledge • Strongest signal of positive selection • Encodes A111T polymorphism associated with pigment differences in humans. • LCT: • 2.4Mb • 24 SNPs fulfill first two criteria • Confer adult persistence of lactase. • Only was identified as functional after extensive study of the LCT gene.

  12. Some specific cases • PS on copy number • Expression differences exist between populations and can confer different fitness advantage and thus be positively selected. • Therefore, positive selection can potentially act on copy number and on non-coding regions. • AMY1: copy number is positively correlated with salivary amylase protein expression. • Mean AMY1 copy was higher in the high-starch population • PS on Noncoding Genomic Regions

  13. Discussion Why have many earlier results fared poorly in genome-wide studies? Red triangles: previous candidates for selection (81) Gray diamonds: newly available genome-wide empirical data set.

  14. Discussion 1.- False positives and negatives 2.- Ascertainment bias of data 3.- Demographic events 4.- Bias DNA repair

  15. Bibliography

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