2007

Melvin Tooker and Paul VanRadenMelvin Tooker and Paul VanRadenAnimal Improvement Programs Lab, USDA, Beltsville, MD, USA

Melvin.Tooker@ars.usda.gov

2009

Happy Bulls, Happy Cows, Happy Bulls, Happy Cows, HaplotypesHaplotypes

Council on Dairy Cattle Breeding, April 2010 (2) Melvin Tooker

What is a Haplotype?What is a Haplotype?

A group of alleles on a single chromosome that are closely linked usually inherited as a unit.

Council on Dairy Cattle Breeding, April 2010 (3) Melvin Tooker

Chromosome to Nucleotide sequenceChromosome to Nucleotide sequence

Council on Dairy Cattle Breeding, April 2010 (4) Melvin Tooker

Example of a SNP haplotypeExample of a SNP haplotype

caacgtat

caacggat

SNP

atccgaat

atccgcat

…

… …

…

SNP

tctaggat

tctcggat

SNP

…

…Chr1

Chr2

Haplotype is a set of single nucleotide polymorphisms (SNPs) associated on a single chromosome. Identification of a few alleles of a haplotype block can identify other polymorphic sites in the region.

Haplotype A tca

gac Haplotype B

Council on Dairy Cattle Breeding, April 2010 (5) Melvin Tooker

Example Bull: O-StyleExample Bull: O-Style

Council on Dairy Cattle Breeding, April 2010 (6) Melvin Tooker

Genotyped Ancestors of OStyleGenotyped Ancestors of OStyleT B Elevat

Elevation Magnet

Bova Chief

Cubby Valiant Elevation

Chief

Manfred Valiant Rocket

Tesk P Iv Star

ggdam Bell Mars Tony

Ivanhoe

O Man P Iv Star Heilo Bell

Bell Chief

Elton Glendell Needle

Glendell

Jezebel Rotate P Comb’n

Melwood Chief

ggdam Mark Bova

Council on Dairy Cattle Breeding, April 2010 (7) Melvin Tooker

Genotyped Ancestors of OStyleGenotyped Ancestors of OStyleElevation

Starbuck Majesty

Aerostar Citation

Rudolph Mattador Valiant

Cavalier

Teamster Ned Boy Chairman

Mascot Tradition

ggdam Leadman Mark

Elevation

Deva Starbuck Chief

Prelude Chairman

Mtoto Blackstar Mark

Valiant

Dima Royalty Bell

Comotion Ned Boy

ggdam Mascot Cleitus

Council on Dairy Cattle Breeding, April 2010 (8) Melvin Tooker

O-Style HaplotypesO-Style Haplotypeschromosome 15chromosome 15

Council on Dairy Cattle Breeding, April 2010 (9) Melvin Tooker

Find Haplotypes – AB codingFind Haplotypes – AB coding

Genotypes:

Oman BB,AA,AA,AB,AA,AB,AB,AA,AA,AB

Ostyle BB,AA,AA,AB,AB,AA,AA,AA,AA,AB

Haplotypes:

OStyle (pat) B A A _ A A A A A _OStyle (mat) B A A _ B A A A A _

Council on Dairy Cattle Breeding, April 2010 (10) Melvin Tooker

Find Haplotypes – 0,1,2 codingFind Haplotypes – 0,1,2 coding

Genotypes: codes 0 = BB, 1 = AB or BA, 2 = AA

Oman 0 2 2 1 2 1 1 2 2 1

Ostyle 0 2 2 1 1 2 2 2 2 1

Haplotypes: codes 0 = B , 1 = unknown, 2 = A

OStyle (pat) 0 2 2 1 2 2 2 2 2 1OStyle (mat) 0 2 2 1 0 2 2 2 2 1

Council on Dairy Cattle Breeding, April 2010 (11) Melvin Tooker

Most Frequent HaplotypesMost Frequent Haplotypes

5.16% 0222222220200200220020202000200002002020000220222222022204.37% 0220202202022000200220222000022002002000002002222000022024.36% 0220200222022002000220202200002202022000022002222002022203.67% 0220202220202220020220222020200002022200002000020200020023.66% 0222222220202220220202002200000202222020000020202200020223.65% 0220200222022002000220202200002202022000022002222002022203.51% 0220022220202220220220202202002220022000000020222200022203.42% 0220022220022200220220202200202002022020002020200200020203.24% 0222222220202000000220202200202002022020002020200200020203.22% 022002222002220022002020002220000202200000202022020202220

Most frequent haplotype in first segment of chromosome 15 for Holsteins had 4,316 copies= 41,822 * 2 * .0516

Council on Dairy Cattle Breeding, April 2010 (12) Melvin Tooker

Imputed DamsImputed Dams

If progeny and sire both genotyped• First progeny inherits 1 of dam’s 2

haplotypes• Second progeny has 50:50 chance to

get same or other haplotype• Haplotypes known with 1, 2, 3, etc.

progeny are ~50%, 75%, 87%, etc.

Council on Dairy Cattle Breeding, April 2010 (13) Melvin Tooker

Applications of HaplotypingApplications of Haplotyping

Imputation of non-genotyped parents

Fill in missing SNPs on genotyped animals by looking at relatives

Imputation of different size SNP chip sets: 3K to 50K