milt thomas, department of animal and range sciences identification of molecular markers to improve...
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Milt Thomas, Department of Animal and Range Sciences
Identification of Molecular Markers to Improve Fertility of Beef Cattle
(USDA-NRI 200835205-18751)
Milt Thomas, Department of Animal and Range Sciences
OutlineI. Molecular markers and research - background. II.Fertility traits in beef cattle –background. III.Evolution of a fertility project. IV.Fertility project specifics.
A. Team of scientists.B. Hypothesis and objectives (I and II).C. Populations.D. Additional efforts.
V. Questions.
Milt Thomas, Department of Animal and Range Sciences
Quantitative Trait Loci (QTL): chromosomal-locus associated with a quantitative trait.
Genetic Marker: unique DNA sequence passed from parent to progeny (molecular alleles).
Marker Assisted Selection (MAS): using genetic marker(s) in selection.
Marker Assisted Management (MAM): using genetic markers for management decisions.
bovineSNP50: a genotyping tool containing ~54,000 SNP across the bovine genome.
gEPD: genetic marker information used in EPD estimation.
Whole Genome Selection (WGS): using genetic markers across the genome in selection
Linkage disequilibrium: non-random association of alleles at 2 or more loci.
Molecular Markers – Background
Important Definitions
Milt Thomas, Department of Animal and Range Sciences
Research approach: QTL Detection
Molecular Markers – Background
Trait = pregnancy rate
http://www.animalgenome.org/QTLdb/cattle.html
Milt Thomas, Department of Animal and Range Sciences
SOCS2 (15.4 Mb)
STAT6 (32.5 Mb)
IGF1 (38 Mb)PMCH (37.7 Mb)
IGFBP6 (20.5 Mb)
STAT2 (33.3 Mb)
LCTN (16.2 Mb)
DeAtley, K. L., G. Rincon, C. R. Farber, J. F. Medrano, R. M. Enns, G. A. Silver, and M. G. Thomas. 2008. Association of microsatellite ETH10 genotypes with growth and carcass trait levels in Brangus cattle. Proc. West. Sect. Am. Soc. Anim. Sci. 59:69-71.
Research approach: Fine mapping/resequencing of genes under a QTL
Molecular Markers – Background
Eth10
Milt Thomas, Department of Animal and Range Sciences
Research approach: identify important/functional markers
Molecular Markers – Background
2006047
GG
2004087
GG
2004102
AG
1993002
GG
2002026
GG
2002001
AG
2000128
AA
ANGUS ANGUS
ANGUS
BRAHMAN1/2 BRAH:1/2 ANGUS
3/4 BRAH:1/4 ANGUS
3/8 BRAH:5/8 ANGUS
Growth and carcass QTL on Chromosome 20.
Growth hormone receptor gene underlies the QTL
Resequenced ~1,000 bp flanking GT-SSR
Discovered A/G tag SNP (ss86273136) segregating in Brangus
Garrett, A.J., G. Rincon, J.F. Medrano, M.A. Elzo, G.A. Silver, and M.G. Thomas. 2008. Promoter region of the bovine growth hormone receptor gene: single nucleotide polymorphisms discovery in cattle and association with performance in Brangus bull. J. Anim. Sci. published ahead of print: doi:10.2527/jas.2008-0990.
Milt Thomas, Department of Animal and Range Sciences
Research approach: association of genotype:phenotype
Molecular Markers – Background
ItemGenotypes Pooled
SE P > FAA AG GG
n 87 283 180
205-d weight, kg 271.85 267.44 273.39 4.37 0.2114
365-d weight, kg 510.34 500.00 499.14 6.07 0.1855
Test ADG, kg/d 1.57 1.52 1.51 0.04 0.1558
Scrotal circumference, cm 35.42 35.14 35.08 0.35 0.3525
Intramuscular fat, % 3.56 3.55 3.64 0.06 0.1202
LM area/BW, cm2/kg 0.17 0.17 0.17 0.002 0.8178
LM area, cm2 81.81 81.27 82.01 1.18 0.6062
Rib fat, cm 0.62 0.62 0.66 0.015 0.0204
Table 4. Least squares means among tag SNP ss86273136 genotypes in the GHR gene in Brangus bulls.
+
Milt Thomas, Department of Animal and Range Sciences
Validation:
Molecular Markers – Background
Milt Thomas, Department of Animal and Range Sciences
Age at puberty: number of Julian days from birth until puberty is achieved (h2 ~0.4).
Age at first calving: number of Julian days from birth until first parturition (~24 mo).
Pregnant as a yearling: pregnant after yearling breeding season (h2 ~0.2; yes or no).
Calving interval: number of days between successive calvings.
Stayability: probability a cow will remain in the herd until six years of age.
Whole herd reporting: data inventory/recording system for each cow each year.
Fertility traits – Background
Important Definitions:
Milt Thomas, Department of Animal and Range Sciences
Reproduction has been described as the most economically relevant component in beef production systems (Willham, 1973 and 1991; Melton, 1995).
National survey results suggest opportunities exist to improve calf survivability and reproductive efficiency in many beef herds (Dargatz et al., 2004).
Genetic improvement programs for reproductive traits have been much slower to develop than for growth and carcass traits due to the difficulty in developing whole-herd data collection systems and the time required to ample data (personal experience with IBBA).
Genetic marker association studies involving fertility are limited as are the number of SNP within dbSNP that are within functional regions of genes (current research program).
Fertility traits – Background
Important Information:
Konni Shirley, Department of Animal and Range Sciences
Trait CC CT TT χ2
P-
value
First observed estrus 61.8 36.4 1.8 30.0 0.01
Estrus at synchronization 66.3 33.7 0 9.1 0.01
Pregnant during 1st breeding season 57.1 41.9 1.0 53.2 0.01
AI pregnancy 66.7 33.3 0 3.3 0.07
Calved by 2 yr of age 59.2 39.8 1.0 51.6 0.01
Percentages of IGF-I genotypes for categorical reproductive trait
Evolution of a Fertility ProjectNBCEC Large Herd Managers Symposium, KC -2005
– Spring born Brangus (n = 190) heifers
– Born 1997 to 2002
– Progeny of 14 Brangus sires
Milt Thomas, Department of Animal and Range Sciences
Evolution of a Fertility ProjectNBCEC Large Herd Managers Symposium, KC -2005
Initial Results from Rex Ranch Project Relative NMSU Angus Heifers
HerdPregnancy
StatusNumber
of Heifers
Genotypic Frequency, %
CC CT TT
1 non-pregnant 160 15 49.4 35.6
1 pregnant 166 19.2 41.6 39.2
3 non-pregnant 75 20 44 36
3 pregnant 85 20 40 40
NMSUPregnancy rate > 90% 110 10 51.8 38.2
Milt Thomas, Department of Animal and Range Sciences
Discussions at the Large Herd Managers helped form a team of scientist with many industry and ag-experiment cooperators.
Identification of Molecular Markers to Improve Fertility of Beef Cattle; USDA-NRI 200835205-18751.
Milt Thomas, PD, New Mexico State University, Reproductive PhysiologyJim Reecy, Co-PD, Iowa State University, Molecular Genetics and BioinformaticsRohan Fernando, Co-PD, Iowa State University, Quantitative Genetics (QTL)Bob Weaber, Supporting Scientist, University of Missouri, Quantitative Genetics John Pollak, Supporting Scientist, Cornell University, Quantitative Genetics
Sunday Peters, Ph.D. student, New Mexico State University, Molecular Biology(Associate Professor, Department of Animal Breeding and Genetics, University of Agriculture, Abeokuta, Nigeria)
Milt Thomas, Department of Animal and Range Sciences
QTL Detection
Validation of MAS tools in commercial
herds across environments and
production systems.
Technology Transfer
Fine Mapping
QTL Detection
Validation of MAS tools in commercial
herds across environments and
production systems.
Technology Transfer
Fine Mapping
Long-term goal: understand in molecular detail the genetic pathways regulating reproductive performance in beef cattle, with the intent of using this information to develop genetic improvement programs for fertility.
Milt Thomas, Department of Animal and Range Sciences
Objective 1: Conduct a SNP-based whole-genome scan to identify QTL associated with heifer pregnancy rate.
Objective 2: Develop data and DNA resources from large commercial beef operations to serve as test populations for validation and technology transfer created by achieving Objective 1 and other future candidate gene association efforts.
Objectives
Identification of Molecular Markers to Improve Fertility of Beef Cattle (USDA-NRI 200835205-18751)
Milt Thomas, Department of Animal and Range Sciences
Objective 1: Conduct a SNP-based whole-genome scan to identify QTL associated with heifer pregnancy rate.
Use Brangus cattle as admixed populationsof livestock have proven useful in detecting QTL.
Relationship fostered from efforts of IBBA –BIC.
Milt Thomas, Department of Animal and Range Sciences
Population for Objective 1: Registered Brangus heifers from Camp Cooley Ranch1.Brangus heifer pregnancy records collected since 1993. 2.DNA and phenotypes on >800 heifers from 54 sires born 2005, 2006, 2007.3.Brangus generation, 4.5 ± 0.044.Trait, pregnant as a yearling, yes (80.6%) or no (19.4%).5.Pregnancy success appears similar among heifers born in the fall vs. spring6.Good success rate with AI.7.Simple statistics for growth and carcass traits:
Birth weight 77.2 ± 0.4 lbs205-day weight 532.2 ± 2.2 lbs365-day weight 799.0 ± 3.3 lbsRibeye area 9.8 ± 0.05 in2
Fat thickness 0.24 ± 0.002 inintramuscular fat % 4.24 ± 0.032 %
0
20
40
60
80
100
Not Pregnant Pregnant
0
10
20
30
40
50
60
70
80
Spring Fall
Number
of Sires
Heifer Pregnancy Percent
0
20
40
60
80
100
Not Pregnant Pregnant
0
10
20
30
40
50
60
70
80
Spring Fall
Number
of Sires
Heifer Pregnancy Percent
Milt Thomas, Department of Animal and Range Sciences
Lab work and Statistical Analyses for Objective 1.
1. DNA extraction of WBC-buffy coat at NMSU.2. bovineSNP50 genotyping (54,000 SNP across the genome).3. QTL detection at ISU using a Bayesian approach (Meuwissen et al.,
2001 and XU, 2003). 4. QTL visualization: QTLdb
Trait = pregnancy rate
http://www.animalgenome.org/QTLdb/cattle.html
Milt Thomas, Department of Animal and Range Sciences
Objective 2: Develop data and DNA resources from large commercial beef operations to serve as test populations for validation and technology transfer created by achieving Objective 1 and other future candidate gene association efforts.
Note: failure of the 1st-calf heifer to rebreed has been considered to be one of the largest economic drains on the beef industry (Clark et al., 2005).
1. Varied production systems and environments which represent the beef industry in the U.S.
2. Obtain resources that could grow into additional trait evaluations (1st calf heifer rebreeding, stayability, etc.)
Milt Thomas, Department of Animal and Range Sciences
Locations of Cooperators (numbers 1-19) and Research Scientists (letters A-D) Working to Study:Identification of Molecular Markers to Improve Fertility in Beef Cattle
1
23
45
6
78
9
10
11
12
1314
15
16
17
18
19
A
B
C
D
Milt Thomas, Department of Animal and Range Sciences
Additional Efforts1. Whole genome breeding value estimates (collaboration with Dorian Garrick, ISU).2. Transcriptome sequencing of important tissues (i.e., hypothalamus-NCGR)
and evaluate bovineSNP50 QTL-SNP relative gene expression loci.
Milt Thomas, Department of Animal and Range Sciences
Identification of Molecular Markers to Improve Fertility of Beef Cattle (USDA-NRI 200835205-18751)
1.Conclusions2.Acknowledgements3.Questions/Discussion
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