K. G. Dodds

Mutations in an oocyte-derived growth factor gene ( BMP15 ) cause increased ovulation rate and infertility in a dosage-sensitive manner

Multiple ovulations are uncommon in humans, cattle and many breeds of sheep. Pituitary gonadotrophins and as yet unidentified ovarian factors precisely regulate follicular development so that, normally, only one follicle is selected to ovulate. The Inverdale (FecXI) sheep, however, carries a naturally occurring X-linked mutation that causes increased ovulation rate and twin and triplet births in heterozygotes (FecXI/FecX+; ref. 1), but primary ovarian failure in homozygotes (FecXI/FecXI; ref. 2). Germ-cell development, formation of the follicle and the earliest stages of follicular growth are normal in FecXI/FecXI sheep, but follicular development beyond the primary stage is impaired. A second family unrelated to the Inverdale sheep also has the same X-linked phenotype (Hanna, FecXH). Crossing FecXI with FecXH animals produces FecXI/FecXH infertile females phenotypically indistinguishable from FecXI/FecXI females. We report here that the FecXI locus maps to an orthologous chromosomal region syntenic to human Xp11.2–11.4, which contains BMP15, encoding bone morphogenetic protein 15 (also known as growth differentiation factor 9B (GDF9B)). Whereas BMP15 is a member of the transforming growth factor β (TGFβ) superfamily and is specifically expressed in oocytes, its function is unknown. We show that independent germline point mutations exist in FecXI and FecXH carriers. These findings establish that BMP15 is essential for female fertility and that natural mutations in an ovary-derived factor can cause both increased ovulation rate and infertility phenotypes in a dosage-sensitive manner.

Highly Prolific Booroola Sheep Have a Mutation in the Intracellular Kinase Domain of Bone Morphogenetic Protein IB Receptor (ALK-6) That Is Expressed in Both Oocytes and Granulosa Cells

Abstract The Booroola fecundity gene (FecB) increases ovulation rate and litter size in sheep and is inherited as a single autosomal locus. The effect of FecB is additive for ovulation rate (increasing by about 1.6 corpora lutea per cycle for each copy) and has been mapped to sheep chromosome 6q23–31, which is syntenic to human chromosome 4q21–25. Bone morphogenetic protein IB (BMP-IB) receptor (also known as ALK-6), which binds members of the transforming growth factor-β (TGF-β) superfamily, is located in the region containing the FecB locus. Booroola sheep have a mutation (Q249R) in the highly conserved intracellular kinase signaling domain of the BMP-IB receptor. The mutation segregated with the FecB phenotype in the Booroola backcross and half-sib flocks of sheep with no recombinants. The mutation was not found in individuals from a number of sheep breeds not derived from the Booroola strain. BMPR-IB was expressed in the ovary and in situ hybridization revealed its specific location to the oocyte and the granulosa cell. Expression of mRNA encoding the BMP type II receptor was widespread throughout the ovary. The mutation in BMPR-IB found in Booroola sheep is the second reported defect in a gene from the TGF-β pathway affecting fertility in sheep following the recent discovery of mutations in the growth factor, GDF9b/BMP15.

Understanding the relationship between the inbreeding coefficient and multilocus heterozygosity: theoretical expectations and empirical data

Geneticists have been interested in inbreeding and inbreeding depression since the time of Darwin. Two alternative approaches that can be used to measure how inbred an individual is involve the use of pedigree records to estimate inbreeding coefficients or molecular markers to measure multilocus heterozygosity. However, the relationship between inbreeding coefficient and heterozygosity has only rarely been investigated. In this paper, a framework to predict the relationship between the two variables is presented. In addition, microsatellite genotypes at 138 loci spanning all 26 autosomes of the sheep genome were used to investigate the relationship between inbreeding coefficient and multilocus heterozygosity. Multilocus heterozygosity was only weakly correlated with inbreeding coefficient, and heterozygosity was not positively correlated between markers more often than expected by chance. Inbreeding coefficient, but not multilocus heterozygosity, detected evidence of inbreeding depression for morphological traits. The relevance of these findings to the causes of heterozygosity–fitness correlations is discussed and predictions for other wild and captive populations are presented.

A second-generation linkage map of the sheep genome.

A genetic map of Ovis aries (haploid n = 27) was developed with 519 markers (504 microsatellites) spanning ∼3063 cM in 26 autosomal linkage groups and 127 cM (female specific) of the X Chromosome (Chr). Genotypic data were merged from the IMF flock (Crawford et al., Genetics 140, 703, 1995) and the USDA mapping flock. Seventy-three percent (370/504) of the microsatellite markers on the map are common to the USDA-ARS MARC cattle linkage map, with 27 of the common markers derived from sheep. The number of common markers per homologous linkage group ranges from 5 to 22 and spans a total of 2866 cM (sex average) in sheep and 2817 cM in cattle. Marker order within a linkage group was consistent between the two species with limited exceptions. The reported translocation between the telomeric end of bovine Chr 9 (BTA 9) and BTA 14 to form ovine Chr 9 is represented by a 15-cM region containing 5 common markers. The significant genomic conservation of marker order will allow use of linkage maps in both species to facilitate the search for quantitative trait loci (QTLs) in cattle and sheep.

Heritability estimates of methane emissions from sheep

The objective of this study was to determine the genetic parameters of methane (CH4) emissions and their genetic correlations with key production traits. The trial measured the CH4 emissions, at 5-min intervals, from 1225 sheep placed in respiration chambers for 2 days, with repeat measurements 2 weeks later for another 2 days. They were fed in the chambers, based on live weight, a pelleted lucerne ration at 2.0 times estimated maintenance requirements. Methane outputs were calculated for g CH4/day and g CH4/kg dry matter intake (DMI) for each of the 4 days. Single trait models were used to obtain estimates of heritability and repeatability. Heritability of g CH4/day was 0.29 ± 0.05, and for g CH4/kg DMI 0.13 ± 0.03. Repeatability between measurements 14 days apart were 0.55 ± 0.02 and 0.26 ± 0.02, for the two traits. The genetic and phenotypic correlations of CH4 outputs with various production traits (weaning weight, live weight at 8 months of age, dag score, muscle depth and fleece weight at 12 months of age) measured in the first year of life, were estimated using bivariate models. With the exception of fleece weight, correlations were weak and not significantly different from zero for the g CH4/kg DMI trait. For fleece weight the phenotypic and genetic correlation estimates were −0.08 ± 0.03 and −0.32 ± 0.11 suggesting a low economically favourable relationship. These results indicate that there is genetic variation between animals for CH4 emission traits even after adjustment for feed intake and that these traits are repeatable. Current work includes the establishment of selection lines from these animals to investigate the physiological, microbial and anatomical changes, coupled with investigations into shorter and alternative CH4 emission measurement and breeding value estimation techniques; including genomic selection.

Economic values for ewe prolificacy and lamb survival in New Zealand sheep

Abstract Economic values of changes in ewe prolificacy (EP) and two lamb survival traits were quantified for situations where each trait is changed by either quantitative genetic selection or the introduction of major genes for prolificacy. The economic value of EP was shown to be highly variable (

Discovery of quantitative trait loci for resistance to parasitic nematode infection in sheep: I. Analysis of outcross pedigrees

11.55 to

Evidence That an Imprinted Gene on the X Chromosome Increases Ovulation Rate in Sheep

24.26 for lambs born per ewe lambing) across farm types. The economic values of the Booroola and Inverdale genes which affect EP also varied substantially from farm to farm. Values ranged from

Genomic scan of selective sweeps in thin and fat tail sheep breeds for identifying of candidate regions associated with fat deposition

5.24 to

Production performance, repeatability and heritability estimates for live weight, fleece weight and fiber characteristics of alpacas in New Zealand.

16.23 per ewe lambing for a single allele of the Booroola gene and from