High-Resolution Human/Goat Comparative Map of the Goat Polled/Intersex Syndrome (PIS): The Human Homologue Is Contained in a Human YAC from HSA3q23

doi:10.1006/geno.1998.5691

Genomics

Volume 56, Issue 1, 15 February 1999, Pages 31-39

https://doi.org/10.1006/geno.1998.5691 Get rights and content

Abstract

The genetic and cytogenetic map around the chromosome 1 region shown to be linked with polledness and intersexuality (PIS) in the domestic goat (Capra hircus) was refined. For this purpose, a goat BAC library was systematically screened with primers from human coding sequences, scraped chromosome 1 DNA, bovine microsatellites from the region, and BAC ends. All the BACs (n= 30) were mapped by fluorescencein situhybridization (FISH) on goat chromosome 1q41–q45. The genetic mapping of 30 new goat polymorphic markers, isolated from these BACs, made it possible to reduce the PIS interval to a region of less than 1 cM on goat chromosome 1q43. The PIS locus is now located between the two genesATP1BandCOP,which both map to 3q23 in humans. Genetic, cytogenetic, and comparative data suggest that the PIS region is now probably circumscribed to an ∼1-Mb DNA segment for which construction of a BAC contig is in progress. In addition, a human YAC contig encompassing the blepharophimosis-ptosis-epicanthus-inversus region was mapped by FISH to goat chromosome 1q43. This human disease, mapped to HSA 3q23 and affecting the development and maintenance of ovarian function, could be a potential candidate for goat PIS.

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Cited by (36)

Histological, molecular and transcriptional analysis of PIS goats
2014, Small Ruminant Research
Citation Excerpt :
The PIS individuals are female homozygotes for the dominant gene P (Polled), determining not only polledness but also disorders of sex development in females, which has been confirmed by cytogenetic (60, XX) and molecular (the absence of the SRY gene crucial to testes development) studies. The PIS locus was identified on chromosome 1q43 (Pailhoux et al., 1997) and its detailed analysis revealed its significant homology to a 100-kb region located at 3q23 in humans (Vaiman et al., 1999) and linked to BPES type I (Blepharophimosis Ptosis Epicanthus Inversus Syndrome Type I), for which the FOXL2 gene dysfunction is responsible. Later studies in goats showed that the female-specific locus, critical to ovary differentiation and associated with an 11.7-kb deletion (Pailhoux et al., 2001), causes PIS.
The aim of the present study was to evaluate the level of gonad masculinization in PIS individuals of different age and the expression profile of genes potentially involved in this process. The study involved a total of eight White Improved goats, 1–12 months of age, with different proportion of Saanen and Alpine genes. A control group of three horned and three polled male kids at an analogous age was included in the study. Molecular analysis showed that all individuals with developmental changes in the reproductive tract were the SRY(−) females, which has already been described in PIS goats. Moreover, the PIS deletion was found in the experimental group individuals. Histological analysis confirmed in seven cases the presence of testes and in one case the presence of ovotestis. The expression pattern of the SOX9 and PISRT1 genes in the gonads obtained from the 1- and 3-month-old individuals with sex reversal as well as from horned and polled male kids at an analogous age was similar, whereas in the hermaphrodite's gonads, transcriptional activity of the SOX9 and PISRT1 genes was not observed. A high mRNA level of PISRT1 was found in the testes of the horned male. So what is the role of the latter in male gonads? Although the molecular cause of the discussed syndrome in goats is known, it seems possible that the effect of this long deletion on the development of reverse phenotype may be more complex.
An update on sheep and goat linkage maps and other genomic resources
2007, Small Ruminant Research
Citation Excerpt :
The first development of the goat map occurred in 1996 with the most recent advance for most chromosomes published in 1998 (Schibler et al., 1998a; Vaiman et al., 1996). The only region that has been mapped in depth is the area flanking the PISRT1 locus on chromosome 1 (Pailhoux et al., 2001; Schibler et al., 2000; Vaiman et al., 1997, 1999b), which was identified without a full genome scan (Vaiman et al., 1996). Despite the incompleteness of the goat genetic map there are several researchers that are actively mapping traits, including QTLs, in goats (Table 4).
The linkage maps of sheep and goats are strikingly disparate in terms of comprehensiveness. Since its inception in 1995, the sheep linkage map has been regularly updated with the most recent version (4.6) released in June 2006. The sex averaged sheep linkage map has essentially complete coverage of the sheep genome, spans approximately 3580 cM, and is comprised of 1374 markers representing 1333 loci. The sheep is unusual among mammals in that the male autosomal map of 3817 cM is significantly longer than the female autosomal map of 3146 cM. About 50% of the male map expansion occurs at the centromeric and telomeric ends of chromosomes. In contrast to the situation for sheep, the most recent version of the goat linkage map, with the exception of the map for chromosome 1, was published in 1998 and is available only as a male map. The goat linkage map spans 2737 cM and is comprised of 307 loci, although many of the chromosomes contain two or more linkage groups. The sheep and goat linkage maps are primarily comprised of anonymous microsatellite markers, derived from sheep or cattle sequences. Most markers on the goat map have also been positioned on the sheep map, and many of the markers on the sheep and goat maps have also been positioned on the bovine linkage maps so the maps from all three species can be readily aligned. Several sheep and goat partial linkage maps have been developed as byproducts of QTL studies but many of these partial linkage maps are not publicly available. Several genomics resources are available for sheep and to a lesser degree, for goats, including genomic and cDNA libraries, a large collection of sheep EST sequences, sheep bacterial artificial chromosome (BAC) end sequences from a library with 12-fold genome coverage, mitochondrial sequence maps for sheep and goats, sheep microarrays, and web sites containing genomics and genetics information for both sheep and goats. In addition, two radiation hybrid panels are available for sheep, and a large-scale public single nucleotide polymorphism (SNP) project will lead to a 20 K sheep SNP chip and a haplotype map. Finally, a large number of trait mapping experiments have been or are currently being conducted in sheep and goats. The high degree of sequence and chromosome conservation between sheep, goats and cattle means that many of the cattle genomic resources will also be highly useful for sheep and goats.
The pathway to femaleness: Current knowledge on embryonic development of the ovary
2005, Molecular and Cellular Endocrinology
Increasing evidence indicates that organogenesis of the ovary is not a passive process arising by default in the absence of the testis pathway. A coordinated interaction is actually in force between somatic cells and female germ cells in embryonic ovaries, thus creating a unique microenvironment that facilitates the formation of follicles. Identification of the functional roles of several novel regulatory elements such as Figα, Foxl2, follistatin, and Wnt4 reveals the complexity of early ovarian organization. Challenges await us to establish the molecular connections of these molecules as well as to discover new candidates in the pathway of early ovarian development.
The telomeric region of BTA18 containing a potential QTL region for health in cattle exhibits high similarity to the HSA19q region in humans
2003, Genomics
We have applied a targeted physical mapping approach, based on the isolation of bovine region-specific large-insert clones using homologous human sequences and chromosome microdissection, to enhance the physical gene map of the telomeric region of BTA18 and to prove its evolutionary conservation. The latter is a prerequisite to exploit the dense human gene map for future positional cloning approaches. Partial sequencing and homology search were used to characterize 20 BACs targeted to the BTA18q2.4-q2.6 region. We used fluorescence in situ hybridization (FISH) to create physical maps of 11 BACs containing 15 gene loci; these BACs served as anchor loci. Using these approaches, 12 new gene loci (CKM, STK13, PSCD2, IRF3, VASP, ACTN4, ITPKC, CYP2B6, FOSB, DMPK, MIA, SIX5) were assigned on BTA18 in the bovine cytogenetic map. A resolved physical map of BTA18q2.4-q2.6 was developed, which encompasses 28 marker loci and a comparative cytogenetic map that contains 15 genes. The mapping results demonstrate the high evolutionary conservation between the telomeric region of BTA18q and HSA19q.
Identification of a Goat Intersexuality-Associated Novel Variant Through Genome-Wide Resequencing and Hi-C
2021, Frontiers in Genetics
Taxonomic status of Chinese blue sheep (Pseudois nayaur): new evidence of a distinct subspecies
2020, Integrative Zoology

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^☆: Sequence data from this article have been deposited with the GenBank Data Library under Accession Nos. G41205–G41228, AF040106, AF40117, AF40119, and AF40120.

^☆☆: G. Gall

¹: To whom correspondence should be addressed. Telephone: 00 1 34652427. Fax: 00 1 34652478. E-mail:[email protected].

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Regular ArticleHigh-Resolution Human/Goat Comparative Map of the Goat Polled/Intersex Syndrome (PIS): The Human Homologue Is Contained in a Human YAC from HSA3q23☆,☆☆

Abstract

Gene

Genomics

Genomics

Theriogenology

The genetic sex on intersexual goats and a probable linkage with the gene for hornlessness

Science

Assignment of bovine synteny groups U27 and U8 to R-banded chromosome 12 and 27, respectively

Hereditas

Intersexuality in domestic mammals

Reprod. Nutr. Dev. Suppl.

Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene

Nature

Microsatellite mapping of a gene affecting horn development inBos taurus.

Nat. Genet.

Cytogenetic investigation in Saanen and Alpine artificial insemination bucks. Identification of a Robertsonian translocation

Genet. Sel. Evol.

SRY recognizes conserved DNA sites in sex-specific promoters

Proc. Natl. Acad. Sci. USA

DNA binding activity of recombinant SRY from normal males and XY females

Science

Chromosome painting with human chromosome specific DNA libraries reveals the extent and the distribution of conserved segments in bovine chromosomes

Cytogenet. Cell Genet.

Male development of chromosomally female mice transgenic for Sry

Nature

Sry interactive proteins: Implication for the mechanisms of sex determination

Cytogenet. Cell Genet.

Mapping the Horns (Ho) locus in sheep: A further locus controlling horn development in domestic animals

J. Hered.

Regular Article
High-Resolution Human/Goat Comparative Map of the Goat Polled/Intersex Syndrome (PIS): The Human Homologue Is Contained in a Human YAC from HSA3q23☆,☆☆