Selection of single nucleotide polymorphisms and genotype quality

  • Slides: 20
Download presentation
Selection of single nucleotide polymorphisms and genotype quality for genomic prediction of genetic merit

Selection of single nucleotide polymorphisms and genotype quality for genomic prediction of genetic merit in dairy cattle Abstr. #524 G. R. Wiggans 1, T. S. Sonstegard 1, P. M. Van. Raden 1, L. K. Matukumalli 1, 2, R. D. Schnabel 3, J. F. Taylor 3, F. S. Schenkel 4, and C. P. Van Tassell 1 1 Agricultural Research Service, United States Department of Agriculture, Beltsville, MD, USA and Computational Biology, George Mason University, Manassas, VA, USA 3 Division of Animal Sciences, University of Missouri, Columbia, MO, USA 4 University of Guelph, ON, Canada 2 Bioinformatics george. wiggans@ars. usda. gov ADSA-ASAS 2008 (1) G. R. Wiggans 2008

Bovine SNP 50 Bead. Chip Bovine Hap. Map Consortium Existing SNP resources SNP discovery

Bovine SNP 50 Bead. Chip Bovine Hap. Map Consortium Existing SNP resources SNP discovery Collaborators and users ADSA-ASAS 2008 (2) G. R. Wiggans 2008

Laboratories & animals genotyped l Bovine Functional Genomics Laboratory, ARS, USDA (Beltsville, MD) 8,

Laboratories & animals genotyped l Bovine Functional Genomics Laboratory, ARS, USDA (Beltsville, MD) 8, 236 l Gene. Seek (Lincoln, NE) l University of Alberta (Edmonton, AB) 1, 325 l University of Missouri (Columbia, MO) 914 l Genetics & IVF Institute (Fairfax, VA) l Illumina (San Diego, CA) ADSA-ASAS 2008 (3) 2, 288 703 116 G. R. Wiggans 2008

Genotypes by breed & sex Breed Female Brown Swiss 3 Holstein 1, 567 Jersey

Genotypes by breed & sex Breed Female Brown Swiss 3 Holstein 1, 567 Jersey 0 All 1, 570 ADSA-ASAS 2008 (4) Male 348 9, 046 589 9, 983 All 351 10, 613 589 11, 553 G. R. Wiggans 2008

SNP filtering & counts l SNP available 58, 336 (including those not supported by

SNP filtering & counts l SNP available 58, 336 (including those not supported by Illumina) l Insufficient average number of beads l Unscorable l Monomorphic in Holsteins l Minor allele frequency (MAF) of <5% 6, 145 Percentage heterozygous different from expected or other scoring issues 282 l 4, 360 5, 734 l Highly correlated l Used for genomic prediction 38, 416 ADSA-ASAS 2008 (5) 1, 389 2, 010 G. R. Wiggans 2008

Bull distribution for unscorable SNP 4, 389 Holstein bulls genotyped ADSA-ASAS 2008 (6) G.

Bull distribution for unscorable SNP 4, 389 Holstein bulls genotyped ADSA-ASAS 2008 (6) G. R. Wiggans 2008

SNP distribution for bulls with unscorable SNP ADSA-ASAS 2008 (7) G. R. Wiggans 2008

SNP distribution for bulls with unscorable SNP ADSA-ASAS 2008 (7) G. R. Wiggans 2008

Identical twins & clones l l l GLC Triton-ETN GLC Triad-ETN GLC Trey-ETN 19

Identical twins & clones l l l GLC Triton-ETN GLC Triad-ETN GLC Trey-ETN 19 348 14 Missing SNP 10 364 5 Comestar Laureat Comestar Loyalty 13 16 2 5 Bermath Monroe Bermath Morgan 160 83 156 76 Granduc Blizzard Granduc Spartan 13 36 10 33 Granduc Performance Granduc Performer 988 8 984 Changes 4 U-of-Minn W Fatal Twyla 2, 272 2, 223 U-of-Minn W Fatal Tabina 116 65 ADSA-ASAS 2008 (8) G. R. Wiggans 2008

Genotyping for same bulls l l l 2 laboratories; 46 bulls; 38, 416 SNP

Genotyping for same bulls l l l 2 laboratories; 46 bulls; 38, 416 SNP unscorable only once w Mean of 792 SNP w Range of 20 to 2, 244 SNP conflict (<0. 003%) w Mean of 0. 9 SNP w Range of 0 to 7 SNP ADSA-ASAS 2008 (9) G. R. Wiggans 2008

Highly correlated SNP l l 4, 286 bulls; 40, 426 SNP Compare each SNP

Highly correlated SNP l l 4, 286 bulls; 40, 426 SNP Compare each SNP with all others with MAF within 2% Count all 9 combinations of 0, 1, and 2 for 2 SNP Assumed highly correlated if only combinations with >21 SNP are 00, 11, and 22 or 20, 11, and 02 ADSA-ASAS 2008 (10) G. R. Wiggans 2008

Highly correlated SNP (cont. ) l l 2, 444 pairs detected and categorized into

Highly correlated SNP (cont. ) l l 2, 444 pairs detected and categorized into 1, 696 groups SNP in group Group sizes 2 1, 450 for highly 3 198 correlated 4 30 SNP 5 10 6 6 7 1 10 1 ADSA-ASAS 2008 (11) Groups G. R. Wiggans 2008

Highly correlated SNP (cont. ) l Distance between autosomal SNP w 65, 531 mean

Highly correlated SNP (cont. ) l Distance between autosomal SNP w 65, 531 mean base pairs between consecutive SNP w 19, 826 base pairs between 1, 199 consecutive highly correlated SNP w 423, 033 base pairs between 469 SNP in group where 1 SNP in group is not consecutive ADSA-ASAS 2008 (12) G. R. Wiggans 2008

Minor allele frequency distribution 38, 416 SNP ADSA-ASAS 2008 (13) G. R. Wiggans 2008

Minor allele frequency distribution 38, 416 SNP ADSA-ASAS 2008 (13) G. R. Wiggans 2008

Heterozygosity differences l SNP different from expected heterozygosity by >7% Chromo. MAF some SNP*

Heterozygosity differences l SNP different from expected heterozygosity by >7% Chromo. MAF some SNP* (%) 15 Hapmap 39475 -BTA-20743 20 18 Actual Expected (%) 39 31 41 72 48 26 ARS-BFGL-NGS-9311 ARS-BFGL-NGS-97477 47 95 50 29 ARS-BFGL-NGS-32567 30 59 42 X* ARS-BFGL-NGS-74090 BTB-01316369 42 22 59 44 49 34 *SNP assigned based on bull homozygosity ADSA-ASAS 2008 (14) G. R. Wiggans 2008

Sex determination l l l 605 SNP on X chromosome and not on Y

Sex determination l l l 605 SNP on X chromosome and not on Y (not in pseudo-autosomal region) Bulls should not be heterozygous Cows (n = 255) w Mean of 229. 6 heterozygous SNP w Range of 133 to 277 heterozygous SNP ADSA-ASAS 2008 (15) G. R. Wiggans 2008

Parentage verification & discovery l l Comparent and progeny SNP if both homozygous If

Parentage verification & discovery l l Comparent and progeny SNP if both homozygous If >200 conflicts found, check every other genotype for one with <30 conflicts w May be parent, progeny, duplicate, clone, or identical twin ADSA-ASAS 2008 (16) G. R. Wiggans 2008

Estimating missing SNP − imputing l l Base population gene frequencies estimated with best

Estimating missing SNP − imputing l l Base population gene frequencies estimated with best linear unbiased prediction Estimates provided for all genotyped animals and ancestors If SNP genotype missing, estimate used if within 0. 2 of 0, 1, or 2 6, 268 genotyped animals w 0. 9 % missing w 45% filled ADSA-ASAS 2008 (17) G. R. Wiggans 2008

Summary l High-density Illumina Bovine. SNP 50 Bead. Chip available l >38, 000 SNP

Summary l High-density Illumina Bovine. SNP 50 Bead. Chip available l >38, 000 SNP available for Holsteins l Genotypes consistent across laboratories l Few parent-progeny genotyping errors found l If parentage error found, correct parent often can be determined ADSA-ASAS 2008 (18) G. R. Wiggans 2008

Summary (cont. ) l SNP on X-chromosome support sex validation l Call rate is

Summary (cont. ) l SNP on X-chromosome support sex validation l Call rate is high and may be improved l Detection of highly correlated SNP revealed probable errors in map locations ADSA-ASAS 2008 (19) G. R. Wiggans 2008

Financial support l l l National Research Initiative grants, USDA Natl. Assoc. of Animal

Financial support l l l National Research Initiative grants, USDA Natl. Assoc. of Animal Breeders (NAAB, Columbia, MO) w ABS Global (De. Forest, WI) w Accelerated Genetics (Baraboo, WI) w Alta (Balzac, AB) w Genex (Shawano, WI) w New Generation Genetics (Fort Atkinson, WI) w Select Sires (Plain City, OH) w Semex Alliance (Guelph, ON) w Taurus-Service (Mehoopany, PA) Agricultural Research Service, USDA ADSA-ASAS 2008 (20) G. R. Wiggans 2008