A genome scan for selection signatures in Taihu pig breeds using next-generation sequencing

Taihu pig breeds are the most prolific breeds of swine in the world, and they also have superior economic traits, including high resistance to disease, superior meat quality, high resistance to crude feed and a docile temperament. The formation of these phenotypic characteristics is largely a result of long-term artificial or natural selection. Therefore, exploring selection signatures in the genomes of the Taihu pigs will help us to identify porcine genes related to productivity traits, disease and behaviour. In this study, we used both intra-population (Relative Extend Haplotype Homozygosity Test (REHH)) and inter-population (the Cross-Population Extend Haplotype Homozygosity Test (XPEHH); F-STATISTICS, F_ST) methods to detect genomic regions that might be under selection process in Taihu pig breeds. As a result, we found 282 (REHH) and 112 (XPEHH) selection signature candidate regions corresponding to 159.78 Mb (6.15%) and 62.29 Mb (2.40%) genomic regions, respectively. Further investigations of the selection candidate regions revealed that many genes under these genomic regions were related to reproductive traits (such as the TLR9 gene), coat colour (such as the KIT gene) and fat metabolism (such as the CPT1A and MAML3 genes). Furthermore, gene enrichment analyses showed that genes under the selection candidate regions were significantly over-represented in pathways related to diseases, such as autoimmune thyroid and asthma diseases. In conclusion, several candidate genes potentially under positive selection were involved in characteristics of Taihu pig. These results will further allow us to better understand the mechanisms of selection in pig breeding.     

Allelic heterogeneity at the equine KIT locus in dominant white (W) horses

White coat color has been a highly valued trait in horses for at least 2,000 years. Dominant white (W) is one of several known depigmentation phenotypes in horses. It shows considerable phenotypic variation, ranging from ~50% depigmented areas up to a completely white coat. In the horse, the four depigmentation phenotypes roan, sabino, tobiano, and dominant white were independently mapped to a chromosomal region on ECA 3 harboring the KIT gene. KIT plays an important role in melanoblast survival during embryonic development. We determined the sequence and genomic organization of the ~82 kb equine KIT gene. A mutation analysis of all 21 KIT exons in white Franches-Montagnes Horses revealed a nonsense mutation in exon 15 (c.2151C>G, p.Y717X). We analyzed the KIT exons in horses characterized as dominant white from other populations and found three additional candidate causative mutations. Three almost completely white Arabians carried a different nonsense mutation in exon 4 (c.706A>T, p.K236X). Six Camarillo White Horses had a missense mutation in exon 12 (c.1805C>T, p.A602V), and five white Thoroughbreds had yet another missense mutation in exon 13 (c.1960G>A, p.G654R). Our results indicate that the dominant white color in Franches-Montagnes Horses is caused by a nonsense mutation in the KIT gene and that multiple independent mutations within this gene appear to be responsible for dominant white in several other modern horse populations.     

Characterization of an alternative splicing by a NAGNAG splice acceptor site in the porcine KIT gene

The KIT gene has been shown to have multiple functions in hematopoiesis, melanogenesis, and gametogenesis. In addition, mutations of this gene cause pigmentation disorders in humans and mice and are responsible for coat color differences in pigs. While characterizing polymorphisms in the porcine KIT gene, we detected alternative splicing (AS) of the NAGNAG splice acceptor site at the boundary of intron 4 and exon 5. This AS event generated the E and I isoforms, characterized by insertion or deletion, respectively, of CAG at the borders of coding sequence. AS patterns measured in tissue samples from two randomly selected animals did not identified any tissue-specific outcomes. Analysis of AS patterns using three breeds demonstrated that Landrace and Large White pigs expressed both the E and I isoforms. In contrast, a subset of specimens from Korean Native Pigs (KNP) yielded a single I isoform. Alignment of the sequence from several species revealed that the region between the branch point sequence (BPS) and 3′ acceptor site is conserved. However, it is appeared that the selection of either the proximal or distal splice site varied between species. To test the breed specificity the NAGNAG splice acceptor site, we constructed two lineages of minigenes from KNP and Landrace pigs harboring breed-specific mutations. The minigene splicing assay demonstrated that both types of minigenes expressed both the E and I isoforms in two host cell lines, and no differences were detected in the AS pattern between the two breeds. We conclude that the AS at the NAGNAG splice acceptor site on intron 4/exon 5 in the porcine KIT gene is the result of noise selection at the splice site by the splicing machinery. Therefore, this AS event in the porcine KIT gene is unlikely to have any relationship with the coat color variations of Landrace and KNP breeds.     

Microsatellite mapping of the bovine roan locus: A major determinant of White Heifer Disease

In the Belgian Blue Cattle breed, coat color variation is mainly under the influence of a single autosomal locus, the roan locus, characterized by a pair of codominant alleles: r ⁺ (black) and R (white). Heterozygous r ⁺ R animals have intermingled black and white hairs, yielding the ``blue' phenotype typical of the breed. Major interest for the roan locus stems from its pleiotropic effect on fertility, owing to the critical role of the R allele in the determinism of White Heifer Disease. We describe the linkage mapping of the roan locus to bovine Chromosome (Chr) 5, in the interval between microsatellite markers BPI and AGLA293, with an associated lodscore of 11.2. Moreover, we map a candidate gene, the Steel locus coding for the mast cell growth factor, to bovine Chr 5. Received: 30 May 1995 / Accepted: 6 September 1995     

Genetic heterogeneity and selection signature at the KIT gene in pigs showing different coat colours and patterns

Mutations in the porcine KIT gene (Dominant white locus) have been shown to affect coat colours and colour distribution in pigs. We analysed this gene in several pig breeds and populations (Sicilian black, completely black or with white patches; Cinta Senese; grey local population; Large White; Duroc; Hampshire; Pietrain; wild boar; Meishan) with different coat colours and patterns, genotyping a few polymorphisms. The 21 exons and parts of the intronic regions were sequenced in these pigs and 69 polymorphisms were identified. The grey-roan coat colour observed in a local grey population was completely associated with a 4-bp deletion of intron 18 in a single copy KIT gene, providing evidence that this mutation characterizes the I^d allele described in the early genetic literature. The white patches observed in black Sicilian pigs were not completely associated with the presence of a duplicated KIT allele (I^p), suggesting that genetic heterogeneity is a possible cause of different coat colours in this breed. Selection signature was evident at the KIT gene in two different belted pig breeds, Hampshire and Cinta Senese. The same mutation(s) may cause the belted phenotype in these breeds that originated in the 18th–19th centuries from English pigs (Hampshire) and in Tuscany (Italy) in the 14th century (Cinta Senese). Phylogenetic relationships of 28 inferred KIT haplotypes indicated two clades: one of Asian origin that included Meishan and a few Sicilian black haplotypes and another of European origin.     

Analysis of ROH patterns in the Noriker horse breed reveals signatures of selection for coat color and body size

Overlapping runs of homozygosity (ROH islands) shared by the majority of a population are hypothesized to be the result of selection around a target locus. In this study we investigated the impact of selection for coat color within the Noriker horse on autozygosity and ROH patterns. We analyzed overlapping homozygous regions (ROH islands) for gene content in fragments shared by more than 50% of horses. Long‐term assortative mating of chestnut horses and the small effective population size of leopard spotted and tobiano horses resulted in higher mean genome‐wide ROH coverage (S_ROH) within the range of 237.4–284.2 Mb, whereas for bay, black and roan horses, where rotation mating is commonly applied, lower autozygosity (S_ROH from 176.4–180.0 Mb) was determined. We identified seven common ROH islands considering all Noriker horses from our dataset. Specific islands were documented for chestnut, leopard spotted, roan and bay horses. The ROH islands contained, among others, genes associated with body size (ZFAT, LASP1 and LCORL/NCAPG), coat color (MC1R in chestnut and the factor PATN1 in leopard spotted horses) and morphogenesis (HOXB cluster in all color strains except leopard spotted horses). This study demonstrates that within a closed population sharing the same founders and ancestors, selection on a single phenotypic trait, in this case coat color, can result in genetic fragmentation affecting levels of autozygosity and distribution of ROH islands and enclosed gene content.     

Genome-Wide Association Study Reveals Genetic Architecture of Eating Behavior in Pigs and Its Implications for Humans Obesity by Comparative Mapping

This study was aimed at identifying genomic regions controlling feeding behavior in Danish Duroc boars and its potential implications for eating behavior in humans. Data regarding individual daily feed intake (DFI), total daily time spent in feeder (TPD), number of daily visits to feeder (NVD), average duration of each visit (TPV), mean feed intake per visit (FPV) and mean feed intake rate (FR) were available for 1130 boars. All boars were genotyped using the Illumina Porcine SNP60 BeadChip. The association analyses were performed using the GenABEL package in the R program. Sixteen SNPs were found to have moderate genome-wide significance (p<5E-05) and 76 SNPs had suggestive (p<5E-04) association with feeding behavior traits. MSI2 gene on chromosome (SSC) 14 was very strongly associated with NVD. Thirty-six SNPs were located in genome regions where QTLs have previously been reported for behavior and/or feed intake traits in pigs. The regions: 64–65 Mb on SSC 1, 124–130 Mb on SSC 8, 63–68 Mb on SSC 11, 32–39 Mb and 59–60 Mb on SSC 12 harbored several signifcant SNPs. Synapse genes (GABRR2, PPP1R9B, SYT1, GABRR1, CADPS2, DLGAP2 and GOPC), dephosphorylation genes (PPM1E, DAPP1, PTPN18, PTPRZ1, PTPN4, MTMR4 and RNGTT) and positive regulation of peptide secretion genes (GHRH, NNAT and TCF7L2) were highly significantly associated with feeding behavior traits. This is the first GWAS to identify genetic variants and biological mechanisms for eating behavior in pigs and these results are important for genetic improvement of pig feed efficiency. We have also conducted pig-human comparative gene mapping to reveal key genomic regions and/or genes on the human genome that may influence eating behavior in human beings and consequently affect the development of obesity and metabolic syndrome. This is the first translational genomics study of its kind to report potential candidate genes for eating behavior in humans.     

SNPs associated with body weight and backfat thickness in two pig breeds identified by a genome-wide association study

Growth and fat deposition are important economic traits due to the influence on production in pigs. In this study, a dataset of 1200 pigs with 345,570 SNPs genotyped by sequencing (GBS) was used to conduct a GWAS with single-marker regression method to identify SNPs associated with body weight and backfat thickness (BFT) and to search for candidate genes in Landrace and Yorkshire pigs. A total of 27 and 13 significant SNPs were associated with body weight and BFT, respectively. In the region of 149.85–149.89 Mb on SSC6, the SNP (SSC6: 149876737) for body weight and the SNP (SSC6: 149876507) for BFT were in the same locus region (a gap of 230 bp). Two SNPs were located in the DOCK7 gene, which is a protein-coding gene that plays an important role in pigmentation. Two SNPs located on SSC8: 54567459 and SSC11: 33043081 were found to overlap weight and BFT; however, no candidate gene was found in these regions. In addition, based on other significant SNPs, two positional candidate genes, NSRP1 and CADPS, were proposed to influence weight. In conclusion, this is the first study report using GBS data to identify the significant SNPs for weight and BFT. A total of four particularly interesting SNPs and one potential candidate genes (DOCK7) were found for these traits in domestic pigs. This study improves our knowledge to better understand the complex genetic architecture of weight and BFT, but further validation studies of these candidate loci and genes are recommended in pigs     

Discovery of selection-driven genetic differences of Duroc,Landrace, and Yorkshire pig breeds by EigenGWAS and Fst analyses

Pigs are one of the earliest domesticated animals and multiple breeds have been developed to meet the various demands of consumers. EigenGWAS is a novel strategy to identify candidate genes that underlying population genetic differences and to infer candidate regions under selection as well. In this study, EigenGWAS and F_st analyses were performed using the public re-sequencing data of three typical commercial pig breeds, Duroc, Landrace and Yorkshire. The intersection of genome-wide significant SNPs detected by EigenGWAS and top-ranked 1% SNPs of F_st results were treated as signals under selection. Using the data of all three breeds, 3062 signals under selection were detected and the nearby genomic regions within 300 kb upstream and downstream covered 6.54% of whole genome. Pairs of breeds were analysed along with the pathway analysis. The gene function enrichment results indicated that many candidate genes located in the genomic regions of the signals under selection were associated with biological processes related to growth, metabolism, reproduction, sensory perception, etc. Among the candidate genes, the FSHB, AHR, PTHLH, KDR and FST genes were reported to be associated with reproductive performance; the KIT, KITLG, MITF, MC1R and EDNRB genes were previously identified to affect coat colour; the RETREG1, TXNIP, BMP5, PPARD and RBP4 genes were reported to be associated with lipid metabolism and growth traits. The identified genetic differences across the three commercial breeds will advance understanding of the artificial selection history of pigs and the signals under selection will suggest potential uses in pig genomic breeding programmes.     

A genome-wide association study for feed efficiency-related traits in a crossbred pig population

Feed efficiency (FE) is one of the most important traits in pig production. However, it is difficult and costly to measure it, limiting the collection of large amount of data for an accurate selection for better FE. Therefore, the identification of single-nucleotide polymorphisms (SNPs) associated with FE-related traits to be used in the genetic evaluation is of great interest of pig breeding programs for increasing the prediction accuracy and the genetic progress of these traits. The objective of this study was to identify SNPs significantly associated with FE-related traits: average daily gain (ADG), average daily feed intake (ADFI) and feed conversion ratio (FCR). We also aimed to identify potential candidate genes for these traits. Phenotypic information recorded on a population of 2386 three-way crossbreed pigs that were genotyped for 51 468 SNPs was used. We identified three loci of quantitative trait (QTL) regions associated with ADG and three QTL regions associated with ADFI; however, no significant association was found for FCR. A false discovery rate (FDR) ≤ 0.005 was used as the threshold for declaring an association as significant. The QTL regions associated with ADG on Sus scrofa chromosome (SSC) 1 were located between 177.01 and 185.47 Mb, which overlaps with the QTL regions for ADFI on SSC1 (173.26 and 185.47 Mb). The other QTL region for ADG was located on SSC12 (2.87 and 3.22 Mb). The most significant SNPs in these QTL regions explained up to 3.26% of the phenotypic variance of these traits. The non-identification of genomic regions associated with FCR can be explained by the complexity of this trait, which is a ratio between ADG and ADFI. Finally, the genes CDH19, CDH7, RNF152, MC4R, PMAIP1, FEM1B and GAA were the candidate genes found in the 1 Mb window around the QTL regions identified in this study. Among them, the MC4R gene (SSC1) has a well-known function related to ADG and ADFI. In this study, we identified three QTL regions for ADG (SSC1 and SSC12) and three for ADFI (SSC1). These regions were previously described in purebred pig populations; however, to our knowledge, this is the first study to confirm the relevance of these QTL regions in a crossbred pig population. The potential use of the SNPs and genes identified in this study in prediction models that combine genomic selection and marker-assisted selection should be evaluated for increasing the prediction accuracy of these traits in this population.     

A genome-wide association analysis for susceptibility of pigs to enterotoxigenic Escherichia coli F41

Enterotoxigenic Escherichia coli (ETEC) is a type of pathogenic bacteria that cause diarrhea in piglets through colonizing pig small intestine epithelial cells by their surface fimbriae. Different fimbriae type of ETEC including F4, F18, K99 and F41 have been isolated from diarrheal pigs. In this study, we performed a genome-wide association study to map the loci associated with the susceptibility of pigs to ETEC F41 using 39454 single nucleotide polymorphisms (SNPs) in 667 F₂ pigs from a White Duroc×Erhualian F₂ cross. The most significant SNP (ALGA0022658, P=5.59×10⁻¹³) located at 6.95 Mb on chromosome 4. ALGA0022658 was in high linkage disequilibrium (r²>0.5) with surrounding SNPs that span a 1.21 Mb interval. Within this 1.21 Mb region, we investigated ZFAT as a positional candidate gene. We re-sequenced cDNA of ZFAT in four pigs with different susceptibility phenotypes, and identified seven coding variants. We genotyped these seven variants in 287 unrelated pigs from 15 diverse breeds that were measured with ETEC F41 susceptibility phenotype. Five variants showed nominal significant association (P<0.05) with ETEC F41 susceptibility phenotype in International commercial pigs. This study provided refined region associated with susceptibility of pigs to ETEC F41 than that reported previously. Further works are needed to uncover the underlying causal mutation(s).     

A missense mutation in the bovine MGF gene is associated with the roan phenotype in Belgian Blue and Shorthorn cattle

The Roan locus is responsible for the coat coloration of Belgian Blue and Shorthorn cattle. The solid-colored and white animals are homozygotes, and the roan animals, with intermingled colored and white hairs, are heterozygous. The roan phenotype was mapped to cattle Chromosome (Chr) 5 with microsatellites, and a candidate gene was proposed (Charlier et al. Mamm Genome 7, 138, 1996). PCR primers to the exons of this candidate gene, the steel locus or mast cell growth factor (MGF) were designed. Solid-colored and white animals were sequenced. A missense mutation at 654 bp (amino acid 193, Ala → Asp) was detected in these two groups. A PCR-RFLP was designed to this single base pair change, and 143 animals in total (Belgian Blue, Shorthorn, and various other breeds) were screened. In addition, the Canadian Beef Cattle Reference Herd (http://skyway.usask.ca/∼schmutz) was used to verify Mendelian inheritance of this marker with the phenotypic inheritance of roan. Our data suggest that this mutation in the bovine MGF gene is responsible for the roan phenotype. Received: 10 December 1998 / Accepted: 26 February 1998     

m6A mRNA methylation regulates the development of gestational diabetes mellitus in Han Chinese women

N6-methyladenosine (m6A) is the most prevalent mRNA modification in mammals. However, m6A modification profiling and its potential role in gestational diabetes mellitus (GDM) have not yet been investigated. In this work, we performed comprehensive m6A analysis in placental tissues from GDM and control patients to elucidate the role of m6A in GDM. An m6A RNA profile identified that m6A levels were strongly decreased in 3′-untranslated regions (UTRs) and coding sequences (CDSs) near stop codons in GDM placenta samples. Among the many methylated mRNAs, MazF-qPCR verified that the m6A levels of the BAMBI 3′-UTR and CDS were significantly decreased in GDM. BAMBI mRNA and protein expression was significantly decreased in GDM, suggesting that m6A plays a key role in regulating gene expression. In addition, it was verified that the m6A levels of GDM related genes (INSR and IRS1) were significantly reduced in GDM. Taken together, our data suggest that down-regulation of m6A both in the 3′-UTR and CDS near stop codons of placental mRNAs is involved in GDM development in Han Chinese women.     

Association study highlights the influence of ELOVL fatty acid elongase 6 gene region on backfat fatty acid composition in Large White pig breed

Dietary fatty acid (FA) composition has an impact on human health. There is an increasing request from consumers for healthier food and pork industry must respond to it without worsening performance and the technological properties of pork products. The inclusion of genetic markers for carcass FA composition in pig selection schemes could be a useful tool to reach the right balance between unsaturated and saturated FAs to satisfy market demands. With the aim of finding genomic regions associated with porcine backfat FA composition, a genome-wide association study was performed on 798 Italian Large White pigs genotyped using Illumina PorcineSNP60 k. The strongest associations with backfat contents of palmitic, palmitoleic, oleic, medium-chain and long-chain FAs were found for the Sus scrofa chromosome (SSC) 8 region located at 119 to 122 Mb, where the gene ELOVL FA elongase 6 is mapped. Palmitic, palmitoleic, stearic and oleic acid contents were also found associated with SSC14, in particular with the genomic region at 121 to 124 Mb, where stearoyl-CoA desaturase Δ9 gene lies. On the other hand, the genomic regions associated with backfat contents of arachidic, arachidonic, n-6 and n-3 FAs showed to harbour mainly genes involved in dietary lipids and carbohydrates digestion, absorption and utilisation. To our knowledge, this is the first study performed in Large White pigs identifying markers and genomic regions associated with backfat FA composition. The results validate in Large White some associations previously detected in other pig breeds and indicate the involvement of distinct metabolic pathways in the deposition pattern of essential and non-essential FAs.     

The Belt mutation in pigs is an allele at the Dominant white (I/KIT) locus

A white belt is a common coat color phenotype in pigs and is determined by a dominant allele (Be). Here we present the result of a genome scan performed using a Hampshire (Belt)/Pietrain (non-Belt) backcross segregating for the white belt trait. We demonstrate that Belt maps to the centromeric region of pig Chromosome (Chr) 8 harboring the Dominant white (I/KIT) locus. Complete cosegregation between Belt and a single nucleotide polymorphism in the KIT gene was observed. Another potential candidate gene, the endothelin receptor type A gene (EDNRA), was excluded as it was assigned to a different region (SSC8q21) by FISH analysis. We argue that Belt is a regulatory KIT mutation on the basis of comparative data on mouse KIT mutants and our previous sequence analysis of the KIT coding sequence from a Hampshire pig. Quantitative PCR analysis revealed that Belt is not associated with a KIT duplication, as is the case for the Patch and Dominant white alleles. Thus, Belt is a fourth allele at the Dominant white locus, and we suggest that it is denoted I ^Be . Received: 5 May 1999 / Accepted: 3 August 1999     

A genome‐wide association analysis for carcass traits in a commercial Duroc pig population

We performed a genome‐wide association study to map the genetic determinants of carcass traits in 350 Duroc pigs typed with the Porcine SNP60 BeadChip. Association analyses were carried out using the gemma software. The proportion of phenotypic variance explained by the SNPs ranged between negligible to moderate (= 0.01–0.30) depending on the trait under consideration. At the genome‐wide level, we detected one significant association between backfat thickness between the 3^rd and 4^th ribs and six SNPs mapping to SSC12 (37–40 Mb). We also identified several chromosome‐wide significant associations for ham weight (SSC11: 51–53 Mb, three SNPs; 67–68 Mb, two SNPs), carcass weight (SSC11: 66–68 Mb, two SNPs), backfat thickness between the 3^rd and 4^th ribs (SSC12: 21 Mb, one SNP; 33–40 Mb, 17 SNPs; 51–58 Mb, two SNPs), backfat thickness in the last rib (SSC12: 37 Mb, one SNP; 40–41 Mb, nine SNPs) and lean meat content (SSC13: 34 Mb, three SNPs and SSC16: 45.1 Mb, one SNP; 62–63 Mb, 10 SNPs; 71–75 Mb, nine SNPs). The ham weight trait‐associated region on SSC11 contains two genes (UCHL3 and LMO7) related to muscle development. In addition, the ACACA gene, which encodes an enzyme for the catalysis of fatty acid synthesis, maps to the SSC12 (37–41 Mb) region harbouring trait‐associated regions for backfat thickness traits. Sequencing of these candidate genes may help to uncover the causal mutations responsible for the associations found in the present study.     

The effect of methyl supplements during pregnancy on the phenotypic modification of offspring agouti coat color in rats

The effect of methyl supplements to the diet of pregnant homozygous (AAHH) female rats with agouti coat color mated with homozygous (aahh) males on the phenotypic modification of the coat color of their heterozygous offspring (AaHh) has been studied. Comparative morphological analysis of the main parameters of hair that determine coat color, including the total length of hairs of different types and the length of the upper black (eumelanin) and light (pheomelanin) parts of awn hairs has been performed. The pattern of pigment granule distribution among hair layers has been analyzed. The melanin content of the hair has been determined using electron spin resonance (ESR). Although all offspring have a typical agouti coat color (alternating black and light portions of hair), 39% of them have a darker coat color than control and other experimental rats have. The main differences between the offspring with darkened and standard coat colors are accounted for by the ratio between the eumelanin and pheomelanin portions of awn hairs. In darkened offspring, this ratio is significantly higher than in control rats. The possible mechanisms of the phenotypic modification of agouti coat color in experimental animals are discussed.     

Pigs with the dominant white coat color phenotype carry a duplication of the KIT gene encoding the mast/stem cell growth factor receptor

Comparative mapping data suggested that the dominant white coat color in pigs may be due to a mutation in KIT which encodes the mast/stem cell growth factor receptor. We report here that dominant white pigs lack melanocytes in the skin, as would be anticipated for a KIT mutation. We found a complete association between the dominant white mutation and a duplication of the KIT gene, or part of it, in samples of unrelated pigs representing six different breeds. The duplication was revealed by single strand conformation polymorphism (SSCP) analysis and subsequent sequence analysis showing that white pigs transmitted two nonallelic KIT sequences. Quantitative Southern blot and quantitative PCR analysis, as well as fluorescence in situ hybridization (FISH) analysis, confirmed the presence of a gene duplication in white pigs. FISH analyses showed that KIT and the very closely linked gene encoding the platelet-derived growth factor receptor (PDGFRA) are both located on the short arm of Chromosome (Chr) 8 at band 8p12. The result revealed an extremely low rate of recombination in the centromeric region of this chromosome, since the closely linked (0.5 cM) serum albumin (ALB) locus has previously been in situ mapped to the long arm (8q12). Pig Chr 8 shares extensive conserved synteny with human Chr 4, but the gene order is rearranged. Received: 22 March 1996 / Accepted: 24 June 1996