The ovine Booroola fecundity gene (FecB) is linked to markers from a region of human chromosome 4q.

The autosomal Booroola fecundity gene (FecB) mutation in sheep increases ovulation rate and litter size, with associated effects on ovarian physiology and hormone profiles. Analysis of segregation in twelve families (379 female progeny) identified linkage between the mutation, two microsatellite markers (OarAE101 and OarHH55, Zmax > 9.0) and epidermal growth factor (EGF) from human chromosome 4q25 (Zmax > 3.0). The marker OarAE101 was linked to secreted phosphoprotein 1 (SPP1, which maps to chromosome 4q21-23 in man) in the test pedigrees and independent families (Zmax > 9.7). The identification of linkage between the FecB mutation and markers from human chromosome 4q is an important step towards further understanding the control of ovulation rates in mammals.

A symmetrical indexing scheme for decagonal quasicrystals analogous to Miller-Bravais indexing of hexagonal crystals.

The problems of redundancy and superfluous indices in indexing the planes and axes in a decagonal quasicrystal are considered, using a scheme of five coplanar vectors in the quasiperiodic plane and one perpendicular vector. Of all the indexing schemes in use, this scheme offers the maximum advantage. An analogy is drawn to the hexagonal system using Miller-Bravais indices. Based on this, a symmetry-based indexing system for decagonal phases is devised that follows a simplified approximate zone law analogous to the exact zone law for the hexagonal case. The indices based on this scheme will be designated as ;Frank indices'. High-symmetry electron diffraction zone-axis patterns as well as powder X-ray diffraction patterns are indexed using Frank indices and compared with those of other indexing schemes.

The Gummelt decagon as a 'quasi unit cell'.

Steinhardt, Jeong, Saitoh, Tanaka, Abe & Tsai [Nature (London) (1998), 396, 55-57] have demonstrated that the structure of decagonal Al-Ni-Co can be built from overlapping clusters of a single type. The structure arises from a decoration of the decagons of a Gummelt covering. The unit (essentially a decagonal prism) was called by Steinhardt et al. a 'quasi unit cell'. In this work, a classification scheme is proposed for 'G patterns'--quasiperiodic patterns obtained by decorating a decagonal quasi unit cell. The classification makes use of the fact that G patterns can also be derived from decoration of a tiling. The tiles are analogues, for decagonal quasiperiodic patterns, of the 'asymmetric units' of a periodic pattern; they provide a simple mode of description and classification of the 'Gummelt-type structures'. Four existing models for decagonal phases are considered from this viewpoint.

Least path criterion (LPC) for unique indexing in a two-dimensional decagonal quasilattice.

The least path criterion or least path length in the context of redundant basis vector systems is discussed and a mathematical proof is presented of the uniqueness of indices obtained by applying the least path criterion. Though the method has greater generality, this paper concentrates on the two-dimensional decagonal lattice. The order of redundancy is also discussed; this will help eventually to correlate with other redundant but desirable indexing sets.

Genetically lean and fat sheep differ in their growth hormone response to growth hormone-releasing factor.

The aim of this study was to compare the ovine growth hormone (oGH) responses of 5 genetically lean and 5 genetically fat 9 month old ram lambs (selected on the basis of their ultrasonic backfat thickness) given two 0.3 micrograms kg-1 liveweight intravenous injections of synthetic human pancreatic GH releasing factor analogue Nle27 hGHRF29 -NH2 (GRF-29) 150 minutes apart. Plasma oGH response curves were analysed using an exponential 2 compartmental model and comparisons made through parallel curve analysis. Plasma oGH levels over 200 ng ml-1 were detected in response to GRF-29. Exponential model parameters indicated that lean lambs had a significantly higher rate of oGH release into the plasma after both consecutive GRF-29 injections, and a significantly lower rate of oGH clearance from the plasma after the second GRF-29 injection only. Significantly smaller peak oGH responses to the second GRF-29 injection were shown by the fat lambs. These results suggest that oGH release is impaired in genetically fat lambs and that either the synthesis of releasable oGH is reduced or the inhibitory tone is greater in the fat lambs. The lean and fat sheep may provide a useful model for the study of hormonal control of factors affecting leanness and fatness.

Characterization and linkage mapping of ten sheep microsatellite markers derived from a sheep x hamster cell hybrid.

A cosmid library has been constructed from a sheep x hamster cell hybrid containing sheep chromosome t1, rob (6;24). Clones containing sheep DNA were identified by hybridizing to a total sheep genomic DNA probe. Small fragments (< 500 bp) containing (AC)n microsatellites were subcloned and sequenced. Ten microsatellite markers were characterized and six were mapped back to chromosomes 6 and 24. The remaining microsatellites mapped to chromosome 26, which was shown to be present in a small proportion of cells of the cell line.

The search for the Booroola (FecB) mutation.

Sheep derived from the Booroola Merino strain carry an autosomal mutation (FecB) that increases ovulation rate and litter size. One approach to characterize the genetic mutation is to locate the gene using positional cloning. The locus has been mapped to a region between genes for secreted phosphoprotein 1 (SPP1) and epidermal growth factor (EGF) on sheep chromosome 6. Analysis of possible candidate genes have excluded a number of genes associated with control of reproduction including genes from chromosome 6. Attempts to define close flanking markers and clone the region of DNA containing the mutation are now in progress. We have cloned additional markers and developed a linkage map showing that the FecB locus maps towards the centromere on chromosome 6. We have developed a yeast artificial chromosome (YAC) library for the sheep and begun screening the library to identify large DNA clones spanning the FecB region. These will be used to locate the mutation and shed light on how the mutation increases ovulation rate in Booroola sheep.

HIV infection among women entering the New York State correctional system.

Human immunodeficiency virus infection is the leading medical problem among prison inmates in several states. In 1988 a blinded seroprevalence study was conducted on 480 New York female prison entrants to determine the prevalence of and risk factors for HIV infection in this population. Ninety (18.8 percent) women were HIV-seropositive. Seroprevalence was highest among women ages 30-39 (25.0 percent) and varied by ethnicity (Hispanics, 29.4 percent; Blacks, 14.4 percent; Whites, 7.1 percent) and residence (New York City, 23.8 percent; Upstate, 5.1 percent). Nearly half (44.9 percent) of the 136 acknowledged intravenous drug users and one-third (33.8 percent) of the 71 women with a positive syphilis serology were HIV-seropositive. There was no difference in fertility histories between seropositive and seronegative women, and two of 21 pregnant women were seropositive. This study led to increased clinical and prevention services for this high-risk population.

Sheep linkage mapping: RFLP markers for comparative mapping studies.

Restriction fragment length polymorphisms (RFLPs) detected using cDNA probes for conserved genes provide an important set of markers that anchor or link syntenic groups in a range of divergent mammalian species. DNA probes from sheep, cattle, pig, human and mouse were screened against sheep DNA samples and 24 new RFLP markers for sheep were identified. Among the loci tested, 22 had a homologue that has been mapped in humans. An RFLP for fibronectin (FN1) was linked to alpha-inhibin (INHA) at a distance of 5cM. The FN1 locus has been assigned to sheep chromosome 2q41-q44 and linkage between FN1 and INHA assigns INHA to the same chromosome in sheep. In addition to the new loci reported here, 28 RFLPs have been published previously by this group and these are collated together with RFLPs published from other laboratories. RFLPs have been reported for 86 loci in sheep. Fifty-four loci have been mapped to 16 different chromosomes.

The application of AFLP fingerprinting to construct a YAC contig containing ADH2 and MTP on sheep chromosome 6.

The low density of genetic markers on livestock maps limits progress in positional cloning projects. We demonstrate a strategy of combining comparative mapping with AFLP fingerprinting to develop physical maps in a defined region of the sheep genome. Sequence tagged sites for alcohol dehydrogenase 2 (ADH2) and microsomal triglyceride transfer protein (MTP) were developed and used to screen a sheep yeast artificial chromosome (YAC) library. Nine YACs were identified containing the microsatellite marker BM1329 and either ADH2 or MTP. Additional markers in the region were not available, and AFLP analysis was developed to identify sheep-specific bands within the YACs to determine their degree of overlap. Fourteen bands common to more than one YAC were analysed and provided the markers necessary to develop a YAC contig containing the three STS markers. One YAC (yac260B5) containing all three markers (ADH2, MTP, and BM1329) was mapped to sheep chromosome 6q1.6-->q1.8 by FISH analysis.

The Booroola fecundity (FecB) gene maps to sheep chromosome 6.

The Booroola (FecB) mutation in sheep is linked to markers from a region of syntenic homology to human chromosome HSA4q, but the chromosomal location in sheep has not been determined. Analysis of linkage in Booroola half-sib pedigrees and 17 full-sib families identified genetic linkage between platelet-derived growth factor receptor-alpha (PDGFRA) and alpha s1-casein (CSN1S1) at 12 cM (Zmax = 9.14) and between PDGFRA and the microsatellite markers BM143 and OarHH55 (Zmax = 6.28 and 3.83, respectively). The microsatellite markers OarAE101 and BM143 and genes from the linkage group (PDGFRA, SPP1, and EGF) were mapped in a partial sheep x hamster somatic cell hybrid panel. All markers identified bands specific to somatic cell hybrids containing the sheep chromosome t1 (rob6;24) or t1q (chromosome 6). In sheep the casein genes alpha s1 (CSN1S1), alpha s2 (CSN1S2), beta (CSN2), and kappa (CSN3) are tightly linked, and CSN2 has been mapped to sheep chromosome 6q23-q31. We conclude that the Booroola mutation is located within a conserved syntenic group that maps to sheep chromosome 6.

The linkage map of sheep Chromosome 6 compared with orthologous regions in other species.

The genetic linkage map of sheep Chromosome (Chr) 6 has been extended to include 35 loci with the addition of 11 RFLP and 12 microsatellite loci. The sex-averaged linkage map now spans 154 cM from phosphodiesterase cyclic GMP beta polypeptide (PDE6B) to OarCP125, an anonymous sheep microsatellite. The male and female map lengths, at 180 cM and 132 cM respectively, did not differ significantly. The physical assignment of PDE6B to Chr 6q33-qter orientates the linkage map on sheep Chr 6 with PDE6B near the telomere and OarCP125 towards the centromere. The order and genetic distances between loci are similar for the sheep Chr 6 and cattle Chr 6 maps, except for the position of the casein genes. The sheep Chr 6 linkage map is also comparable to portions of human Chr 4, mouse Chrs 5 and 3, and pig Chr 8. The synteny between sheep Chr 6 and human Chr 4 has been extended from PDE6B (4p16.3) to epidermal growth factor (EGF, 4q25-q27). However, a region from platelet-derived growth factor receptor alpha polypeptide (PDGFRA) to bone morphogenetic protein 3 (BMP3), which spans 19 cM on sheep Chr 6, appears to be inverted with respect to the human and mouse loci. Other differences in the gene order between sheep, pig, and mouse suggest more complex rearrangements.

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.