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K G Dodds

Publications and source records attributed to K G Dodds.

At least 19 recordsLinked to original sources

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.

Animals↗

Bone density in sheep: genetic variation and quantitative trait loci localisation.

Bone density (BD) is an important factor in osteoporotic fracture risk in humans. However, BD is a complex trait confounded by environmental influences and polygenic inheritance. Sheep provide a potentially useful model for studying differences in BD, as they provide a means of circumventing complex environmental factors and are a similar weight to humans. The aims of this study were to establish whether there is genetic variation in BD in sheep and then to localise quantitative trait loci (QTLs) associated with this variation. We also aimed to evaluate the relationship between fat and muscle body components and BD in sheep. Results showed that there was significant (P < 0.01) genetic variation among Coopworth sheep sires for BD. This genetic difference was correlated (P < 0.01) with body weight and muscle mass. A number of QTLs exceeding the suggestive threshold were identified (nine in total). Of these, two (chromosomes 1, P < 0.05; chromosome 24, P < 0.01) were significant using genome-wide permutation significance thresholds (2000 iterations). The position of the QTL on chromosome 24 coincided with a number of other body composition QTLs, indicating possible pleiotropic effects or the presence of multiple genes affecting body composition at that site. This study shows that sheep are potentially a useful model for studying the genetics of BD.

Animals↗

Linkage disequilibrium in domestic sheep.

The last decade has seen a dramatic increase in the number of livestock QTL mapping studies. The next challenge awaiting livestock geneticists is to determine the actual genes responsible for variation of economically important traits. With the advent of high density single nucleotide polymorphism (SNP) maps, it may be possible to fine map genes by exploiting linkage disequilibrium between genes of interest and adjacent markers. However, the extent of linkage disequilibrium (LD) is generally unknown for livestock populations. In this article microsatellite genotype data are used to assess the extent of LD in two populations of domestic sheep. High levels of LD were found to extend for tens of centimorgans and declined as a function of marker distance. However, LD was also frequently observed between unlinked markers. The prospects for LD mapping in livestock appear encouraging provided that type I error can be minimized. Properties of the multiallelic LD coefficient D' were also explored. D' was found to be significantly related to marker heterozygosity, although the relationship did not appear to unduly influence the overall conclusions. Of potentially greater concern was the observation that D' may be skewed when rare alleles are present. It is recommended that the statistical significance of LD is used in conjunction with coefficients such as D' to determine the true extent of LD.

Animals↗

Coriander spice oil: effects of fruit crushing and distillation time on yield and composition.

Crushing intensity and distillation time were evaluated for their effects on the oil yield and composition of steam-distilled essential oil from fruits of Coriandrum sativum var. microcarpum L. A comparison of oils produced by laboratory- and pilot-scale stills showed that the two still types gave comparable yields and oil composition. The laboratory still was then used to compare oil yields and compositions from fruits crushed at three different intensities, at intervals during a distillation period of 60 min. Both crushing intensity and distillation time had significant (P< 0.05) effects on the yield and composition of the oil. The maximum oil yield was less from the light-crushed fruits, but the rate of oil recovery was significantly P < 0.05) higher. From the light-crushed fruits, 95% of the maximum yield was extracted in 22.5 min compared with 32 and 39 min for the standard and heavy-crushed fruits, respectively. The effect of crushing intensity on oil composition was most pronounced on the low-boiling-point a-pinene and on the higher-boiling-point geranyl acetate. Crushing had little effect on linalool content, but distillation time could be manipulated to alter the linalool content of the oil.

Acyclic Monoterpenes↗

Evidence that an imprinted gene on the X chromosome increases ovulation rate in sheep.

Ovulation rate records from 1311 female progeny of 50 Coopworth rams were used to study the inheritance of ovulation rate in a screened high prolificacy sheep flock. Breeding values (BV) for ovulation rate for 33 sires used within the screened flock and ovulation rate deviations for a further 17 sires progeny tested in commercial flocks suggest that a major gene (WOODLANDS: gene) for ovulation rate with a non-Mendelian inheritance pattern is segregating in a family line. Rams assigned as carriers of the putative gene did not produce carrier sons (zero of three), and this coupled with the observation that daughters of carrier rams had ovulation rates of 0. 39 (standard error of difference [SED] = 0.06) higher than contemporaries without a significant increase in the variance of log ovulation rate strongly suggests that the gene is on the X chromosome. The evidence suggests that the gene is also maternally imprinted because ovulation rate data indicate that it is expressed where females inherit a paternal allele but is silenced when inherited on a maternal allele. Maternal granddaughters of carrier rams had mean ovulation rates that were only 0.02 (SED = 0.06) higher than noncarrier ewes from the same flock. Furthermore, carrier dams expressing the gene (paternal allele) had 24 sons, none of which had female offspring that expressed the gene, whereas carrier dams not expressing the gene (maternal allele) had 7 out of 17 sons that had female progeny expressing the gene. There is no evidence of the infertility that occurs in homozygous ewes carrying the X-linked Inverdale gene. Collectively, these results suggest the existence of a novel gene for prolificacy located on the X chromosome that is maternally imprinted. The WOODLANDS: gene was only expressed upon paternal inheritance from carrier males that were the progeny of nonexpressing carrier dams. The gene was not expressed in ewes that received it from either carrier dams (expressing or nonexpressing) or from carrier males that were the progeny of expressing carrier dams.

Animals↗

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.

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-beta (TGF-beta) 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-beta pathway affecting fertility in sheep following the recent discovery of mutations in the growth factor, GDF9b/BMP15.

Activin Receptors↗

An enhanced linkage map of the sheep genome comprising more than 1000 loci.

A medium-density linkage map of the ovine genome has been developed. Marker data for 550 new loci were generated and merged with the previous sheep linkage map. The new map comprises 1093 markers representing 1062 unique loci (941 anonymous loci, 121 genes) and spans 3500 cM (sex-averaged) for the autosomes and 132 cM (female) on the X chromosome. There is an average spacing of 3.4 cM between autosomal loci and 8.3 cM between highly polymorphic [polymorphic information content (PIC) > or = 0.7] autosomal loci. The largest gap between markers is 32.5 cM, and the number of gaps of > 20 cM between loci, or regions where loci are missing from chromosome ends, has been reduced from 40 in the previous map to 6. Five hundred and seventy-three of the loci can be ordered on a framework map with odds of > 1000 : 1. The sheep linkage map contains strong links to both the cattle and goat maps. Five hundred and seventy-two of the loci positioned on the sheep linkage map have also been mapped by linkage analysis in cattle, and 209 of the loci mapped on the sheep linkage map have also been placed on the goat linkage map. Inspection of ruminant linkage maps indicates that the genomic coverage by the current sheep linkage map is comparable to that of the available cattle maps. The sheep map provides a valuable resource to the international sheep, cattle, and goat gene mapping community.

Animals↗

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 beta (TGFbeta) 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.

Amino Acid Sequence↗

Genetic resistance to experimental infection with Mycobacterium bovis in red deer (Cervus elaphus).

Tuberculosis (Tb) caused by Mycobacterium bovis is a worldwide threat to livestock and humans. One control strategy is to breed livestock that are more resistant to Mycobacterium bovis. In a 3-year heritability study 6 farmed red deer stags were selected from 39 on the basis of their differing responses to experimental challenge via the tonsillar sac with approximately 500 CFU of M. bovis. Two stags remained uninfected, two were moderately affected, and two developed serious spreading Tb. Seventy offspring, bred from these six stags by artificial insemination using stored semen, were similarly challenged with M. bovis. The offspring showed patterns of response to M. bovis challenge similar to those of their sires, providing evidence for a strong genetic basis to resistance to Tb, with an estimated heritability of 0.48 (standard error, 0.096; P < 0. 01). This is the first time the heritability of Tb resistance in domestic livestock has been measured. The breeding of selection lines of resistant and susceptible deer will provide an ideal model to study the mechanisms of Tb resistance in a ruminant and could provide an additional strategy for reducing the number and severity of outbreaks of Tb in farmed deer herds. Laboratory studies to identify genetic and immunological markers for resistance to Tb are under way. Preliminary studies showed no associations between NRAMP or DRB genes and resistance to Tb in deer. Patterns of immune responses seen in resistant animals suggest that both innate and acquired pathways of immunity are necessary to produce the resistant phenotype.

Animals↗

Catalase gene is associated with facial eczema disease resistance in sheep.

Facial eczema (FE) is a hepatogenous photosensitization disease of ruminant animals, particularly in sheep which vary widely in their susceptibility to the disease. The liver damage is caused by the mycotoxin, sporidesmin. There is evidence that the toxicity of sporidesmin is due to its ability to generate 'active oxygen' species. We evaluated the catalase gene, which encodes an enzyme with antioxidant functions, as a candidate for determining the susceptibility of sheep to the disease. Two microsatellite markers, OarSHP3 and OarSHP4, which flank the sheep catalase gene, were isolated from a Yeast Artificial Chromosome (YAC) clone. These markers mapped the catalase locus by linkage to ovine chromosome 15. Eleven informative markers spaced throughout chromosome 15, inclusive of the catalase marker OarSHP4, gave no significant linkage with the disease traits when analysed in four outcross resource pedigrees. However, OarSHP3 and OarSHP4 allele frequencies showed significant differences between FE resistant and susceptible selection-lines. Comparison of sequences of catalase cDNAs from sheep of resistant and susceptible lines showed only two silent mutations. A single nucleotide polymorphisms (KP1) in exon 6 of the catalase gene also showed significant differences in allele frequencies between the selection lines. The lack of evidence for linkage in outcross pedigrees, but the significant association in the genetic lines, implies that catalase is involved in determining the susceptibility of sheep to facial eczema, and that the candidate gene's effect is probably recessive or minor.

Alleles↗

Microsatellite evolution: testing the ascertainment bias hypothesis.

Previous studies suggest the median allele length of microsatellites is longest in the species from which the markers were derived, suggesting that an ascertainment bias was operating. We have examined whether the size distribution of microsatellite alleles between sheep and cattle is source dependent using a set of 472 microsatellites that can be amplified in both species. For those markers that were polymorphic in both species we report a significantly greater number of markers (P < 0.001) with longer median allele sizes in sheep, regardless of microsatellite origin. This finding suggests that any ascertainment bias operating during microsatellite selection is only a minor contributor to the variation observed.

Animals↗

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 approximately 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.

Animals↗

Seasonal effects on gestation length and birth weight in alpacas.

Gestation lengths and birth weights were measured in 162 pregnancies in alpacas (Lama pacos) farmed in the high country of the South Island of New Zealand. A comparison of pregnancies from spring (mid-October to mid-December) and autumn (mid-February to late April) matings showed that gestation lengths were 12.5 days longer in spring (348.9 +/- 1.4 days vs. 336.4 +/- 1.2 days; P < 0.0001). For each day later in spring that a female was mated there was an increase in gestation length of 0.11 days (P < 0.05), whereas for each day later in autumn the gestation was reduced by 0.24 days. There were no significant effects of sex of cria or age of dam on gestation length. After adjustment for gestation length, crias born in autumn weighed 1.0 kg more than those born in spring (8.8 +/- 0.15 kg vs. 7.8 +/- 0.18 kg: P < 0.001). Female crias weighed 0.4 kg less than males at birth (P < 0.05). The results suggest that in this environment it will be difficult to maintain spring-mated females in a 12 month breeding cycle.

Animals↗