Mapping of the bovine blood group systems J,N', R', and Z show evidence for oligo-genetic inheritance

Genes determining the bovine erythrocyte antigens were mapped by linkage analysis. In total 9591 genotypes of 20 grandsire families with 1074 sires from a grand-daughter design were elucidated for the genes determining the erythrocyte antigens EAA, EAB, EAC, EAF, EAJ, EAL, EAM, EAN', EAR', EAS, EAT', and EAZ according to standard paternity testing procedures in the blood typing laboratories. Linkage analyses were performed with 248 microsatellite markers, eight SSCP markers and four polymorphic proteins and enzymes covering the 29 autosomes and the pseudoautosomal region of the sex chromosomes. The number of informative meioses for the blood group systems ranged from 76 to 947. Blood group systems EAM and EAT' were non-informative. Most of the erythrocyte antigen loci showed significant linkage to a single chromosome and were mapped unequivocally. The genes determining erythrocyte antigen EAA, EAB, EAC, EAL, and EAS were mapped to chromosomes 15, 12, 18, 3, and 21, respectively. Lod-score values ranged from 11.43 to 107.83. Moreover, the EAF system could be mapped to chromosome 17. However, the EAN' system previously known as part of the EAF system could be mapped to chromosome 5. In addition, the blood group systems EAJ, the new EAN', EAR', and EAZ, showed significant linkage to microsatellite markers on various chromosomes and also to other blood groups. The appearance of a single blood group system might be therefore either dependent on the existence of other blood group systems or because of an interaction between different loci on various chromosomes as is known in humans and in pigs.     

Linkage of bovine erythrocyte antigen loci B, C, L, S, Z, R' and T' and the serum protein loci post-transferrin 2 (PTF 2), vitamin D binding protein (GC) and albumin (ALB) to DNA microsatellite markers

Seven bovine erythrocyte antigen loci and three serum protein loci were tentatively assigned to chromosomes or synteny groups by linkage analysis to previously assigned microsatellite DNA markers. The erythrocyte antigen locus EAB was mapped to synteny group U27; EAC to chromosome 18, synteny group U9; EAL to chromosome 3, synteny group U6; EAS to chromosome 21, synteny group U4; EAZ to chromosome 10, synteny group U5; EAR' to chromosome 16, synteny group U1; and EAT' to chromosome 19, synteny group U21. The vitamin D binding protein (GC) and albumin (ALB) loci were assigned to chromosome 6, synteny group U15 and post-transferrin 2 (PTF 2) to chromosome 19, synteny group U21.     

Index, Comprehensive Microsatellite, and Unified Linkage Maps of Human Chromosome 14 with Cytogenetic Tie Points and a Telomere Microsatellite Marker

Three sets of linkage maps (index, comprehensive microsatellite, and unified) have been constructed for human chromosome 14 based on genotypes from the CEPH reference pedigrees. The index maps consist of 18 microsatellite markers, with heterozygosities of at least 68% and intermarker spacing no greater than 11 cM. The sex-average comprehensive microsatellite map is 125 cM in length and includes 115 markers with 54 loci uniquely placed with odds for marker order of at least 1000:1. The sex-average index map length is 121 cM, and the female- and male-specific maps are 143 and 101 cM, respectively. A unified map was also constructed from 147 loci (162 marker systems), which includes 32 RFLP markers in addition to the 115 microsatellites. The sex-average length of the unified map is 128 cM with 69 loci uniquely placed. Our maps are anchored by a microsatellite telomere marker sCAW1 (D14S826), developed from a telomere YAC clone TYAC196, which extends the linkage map to the physical terminus of the long arm of chromosome 14. Furthermore, we have also physically mapped seven of the loci by fluorescencein situhybridization of cosmid clones orAlu-PCR products amplified from YACs containing the marker sequences. Together with previously established cytogenetic map designations for other loci, our maps display links between genetic markers for 10 of 13 cytogenetic bands of chromosome 14 at the 550 genome band resolution.     

A genetic map of DNA loci on bovine chromosome 1

We constructed a genetic map of most of the length of bovine chromosome 1 using the CSIRO and the Texas A&M University cattle reference families. Twelve loci are in a single linkage group, 9 of which are highly polymorphic loci. Four loci are of known biochemical function, α-1 crystallin (CRYA1), γ-s crystallin (CRYGS), superoxide dismutase 1 (SOD1), and uridine monophosphate synthase (LIMPS), and these have also been previously mapped in humans. The loci CRYA 1, CSRD 1613, GMBT 7, RM 95, SOD I, and LIMPS had been previously assigned to bovine syntenic group U10, while CSRD 1613 and LIMPS had also been assigned to chromosome 1 by in situ hybridization. All of the loci show statistically significant linkage to at least one other locus. The conserved loci indicate that there have been major rearrangements during the evolution of bovine chromosome 1 compared to other mammalian chromosomes. The estimate of the total length of the linkage group is 168 cM, which accords well with the predicted length based on chiasmata frequencies for the bovine genome and the relative size of chromosome 1 in the bovine genome.     

The porcine intestinal receptor for Escherichia coli K88ab,K88ac: regional localization on chromosome 13 and influence of IgG response to the K88 antigen

The loci encoding the porcine intestinal receptors for Escherichia coli K88ab and K88ac (K88abR and K88acR) were firmly assigned to chromosome 13 by linkage analysis using a three-generation pedigree. The linear order of these loci and seven other markers on chromosome 13 was determined by multipoint analyses. The K88abR and K88acR loci were tightly linked with the K88abR locus localized 7·4 cM (sex average) proximal to the transferrin locus. The results, together with previous reports from two other groups, provide an unequivocal assignment of the K88 receptor loci to chromosome 13, and reject a previous assignment to chromosome 4. Pigs possessing the receptor had a slightly higher specific IgG response to the K88 antigen after an intramuscular immunization with an E. coli vaccine.     

Mapping of facioscapulohumeral muscular dystrophy gene to chromosome 4q35-qter by multipoint linkage analysis and in situ hybridization

We have recently assigned the facioscapulohumeral muscular dystrophy (FSHD) gene to chromosome 4 by linkage to the microsatellite marker Mfd 22 (locus D4S171). We now report that D4S139, a VNTR locus, is much more closely linked to FSHD. Two-point linkage analysis between FSHD and D4S139 in nine informative families showed a maximum combined lod score (Z_max) of 17.28 at a recombination fraction θ of 0.027. Multipoint linkage analysis between FSHD and the loci D4S139 and D4S171 resulted in a peak lod score of 20.21 at 2.7 cM from D4S139. Due to the small number of recombinants found with D4S139, the position of the FSHD gene relative to that of D4S139 could not be established with certainty. D4S139 was mapped to chromosome 4q35-qter by in situ hybridization, thus firmly establishing the location of the FSHD gene in the subtelomeric region of chromosome 4q. One small family yielded a negative lod score for D4S139. In the other families no significant evidence for genetic heterogeneity was obtained. Studies of additional markers and new families will improve the map of the FSHD region, reveal possible genetic heterogeneity, and allow better diagnostic reliability.     

Improved carrier testing for multiple endocrine neoplasia,type 1, using new microsatellite-type DNA markers

Familial multiple endocrine neoplasia, type 1 (FMEN1), is an autosomal dominant trait generated by hyperfunction of various endocrine glands. The gene for MEN1 has been mapped to chromosome 11q13 by genetic linkage and deletion mapping in tumors. Eight Finnish families, including 46 individuals carrying the risk haplotype, have been typed for four polymorphic microsatellite DNA markers spanning the MEN1 chromosomal region. Three of the loci concerned, D11S913, D11S987, and D11S1337, displayed maximum lod scores (Z _max ) 6.70, 9.88, and 2.54, respectively, with no recombinations with the disease gene, whereas a Z _max of 8.43 was obtained for D11S971 at a recombination fraction of 0.03. Our results indicate that the use of this set of markers considerably improves the diagnostic value of genotyping patients at risk of developing MEN1.     

The Gene for the Retinal Pigment Epithelium-Specific Protein RPE65 Is Localized to Human 1p31 and Mouse 3

The human and murine chromosomal localization for the gene for the retinal pigment epithelium-specific protein RPE65 was determined. Using interspecific backcross analysis, we mapped Rpe65 to the distal end of mouse chromosome 3. In the human, using a human-hamster hybrid panel, RPE65 was mapped to chromosome 1. By the use of fluorescence in situ hybridization, this localization was refined to 1p31. The mouse and human loci for this potential candidate gene for hereditary retinal disease do not match those of any known disease in mouse or man.     

Mapping of a novel autosomal recessive hypotrichosis locus on chromosome 10q11.23–22.3

Autosomal recessive hypotrichosis is a rare form of human genetic disorder characterized by sparse to absent hair on scalp and rest of the body of affected individuals. Over the past few years at least five autosomal recessive forms of hypotrichosis loci have been mapped on different human chromosomes. In the present study, we report localization of another novel autosomal recessive hypotrichosis locus on human chromosome 10q11.23–22.3 in a four generation consanguineous Pakistani family. All the four patients in the family showed typical features of hereditary hypotrichosis including sparse hair on the scalp and rest of the body. Human genome scan using highly polymorphic microsatellite markers mapped the disease locus to a large region on chromosome 10. This novel locus maps to 29.81 cM (28.5 Mb) region, flanked by markers D10S538 and D10S2327 on chromosome 10q11.23–22.3. A maximum multipoint LOD score of 3.26 was obtained with several markers in this region. DNA sequence analysis of exons and splice-junction sites of four putative candidate genes (P4HA1, ZNF365, ZMYND17, MYST4), located in the linkage interval, were sequenced but were negative for functional sequence variants.     

A comprehensive linkage map of the pig based on a wild pig - Large White intercross

A comprehensive linkage map, including 236 linked markers with a total sex-average map length of about 2300 cM, covering nearly all parts of the pig genome has been established. Linkage groups were assigned to all 18 autosomes, the X chromosome and the X/Y pseudoautosomal region. Several new gene assignments were made including the assignment of linkage group U1 (EAK-HPX) to chromosome 9. The linkage map includes 77 type I loci informative for comparative mapping and 72 in situ mapped markers physically anchoring the linkage groups on chromosomes. A highly significant heterogeneity in recombination rates between sexes was observed with a general tendency towards an excess of female recombination. The average ratio of female to male recombination was estimated at 1–4:1 but this parameter varied between chromosomes as well as between regions within chromosomes. An intriguing finding was that blood group loci were overrepresented at the distal ends of linkage groups.     

Linkage mapping and fluorescence in situ hybridization of TCTE1 on human chromosome 6p: Analysis of dinucleotide polymorphisms on native gels

Highly informative dinucleotide repeat polymorphisms were identified at the T-complex-associated-testes-expressed-1 (TCTE1) locus on human chromosome 6p. Electrophoresis of single-stranded DNA on native gels facilitated the analysis of the dinucleotide polymorphisms. Linkage mapping positions this marker midway between the centromere and HLA with recombination fractions as follows: D6Z1-0.21-TCTE1-0.24-HLA. Two-color fluorescence in situ hybridization places TCTE1 proximal to CRIL171 (D6S19). Together, linkage and in situ hybridization indicate that the order of the loci is D6Z1-D6S4-D6S90-TCTE1-D6S19-D6S29-HLA-telomere. A sequence tagged site (STS) was established, and three yeast artificial chromosome (YAC) clones were identified for the TCTE1 locus.     

Microsatellite mapping of <Emphasis Type="Italic">Ae. speltoides</Emphasis> and map-based comparative analysis of the S,G, and B genomes of Triticeae species

The first microsatellite linkage map of Ae. speltoides Tausch (2n = 2x = 14, SS), which is a wild species with a genome closely related to the B and G genomes of polyploid wheats, was developed based on two F₂ mapping populations using microsatellite (SSR) markers from Ae. speltoides, wheat genomic SSRs (g-SSRs) and EST-derived SSRs. A total of 144 different microsatellite loci were mapped in the Ae. speltoides genome. The transferability of the SSRs markers between the related S, B, and G genomes allowed possible integration of new markers into the T. timopheevii G genome chromosomal maps and map-based comparisons. Thirty-one new microsatellite loci assigned to the genetic framework of the T. timopheevii G genome maps were composed of wheat g-SSR (genomic SSR) markers. Most of the used Ae. speltoides SSRs were mapped onto chromosomes of the G genome supporting a close relationship between the G and S genomes. Comparative microsatellite mapping of the S, B, and G genomes demonstrated colinearity between the chromosomes within homoeologous groups, except for intergenomic T6A^tS.1G, T4AL.5AL.7BS translocations. A translocation between chromosomes 2 and 6 that is present in the T. aestivum B genome was found in neither Ae. speltoides nor in T. timopheevii. Although the marker order was generally conserved among the B, S, and G genomes, the total length of the Ae. speltoides chromosomal maps and the genetic distances between homoeologous loci located in the proximal regions of the S genome chromosomes were reduced compared with the B, and G genome chromosomes.     

Chromosomal assignment of seventeen porcine microsatellites and genes by use of a somatic cell hybrid mapping panel

Swine-specific sequence tagged (microsatellite) sites, STS and STMS, were assigned chromosomally by polymerase chain reaction analysis of a somatic cell hybrid panel. This study confirms the localization from genetic mapping of seven anonymous microsatellites and the genes ANPEP, ATP2, CGA, DAGK, FSHB, IFNG, IGF1, IL1B and SPP1. New assignment for the gene BNP1 to chromosome 6 is reported. The confirmed and the new assignments extend the information of the previously established linkage maps and provide framework loci on which to order additional informative markers.     

Integrated High-Resolution BAC, P1, and Transcript Map of the CHH Region in Chromosome 9p13

A bacterial artificial chromosome (BAC) and P1 contig of the proximal part of chromosome 9p centromeric of markers D9S165 and D9S304 is described. This 1.1- to 1.7-Mb portion of chromosome 9p13 was previously not physically mapped. It contains 24 genes or expressed sequence tags, five polymorphic AC repeats, and three new polymorphic single-strand conformation polymorphism variants. Several of the genes thus mapped are excellent candidates for disease-causing genes whose loci have previously been assigned to proximal 9p. Our primary interest is in the cartilage-hair hypoplasia gene (CHH) that resides within the contig between markers D9S163 and D9S1791 based on linkage evidence.     

High-density genetic and physical bin mapping of wheat chromosome 1D reveals that the powdery mildew resistance gene <Emphasis Type="Italic">Pm24</Emphasis> is located in a highly recombinogenic region

Genetic maps of wheat chromosome 1D consisting of 57 microsatellite marker loci were constructed using Chinese Spring (CS) × Chiyacao F₂ and the International Triticeae Mapping Initiative (ITMI) recombinant inbred lines (RILs) mapping populations. Marker order was consistent, but genetic distances of neighboring markers were different in two populations. Physical bin map of 57 microsatellite marker loci was generated by means of 10 CS 1D deletion lines. The physical bin mapping indicated that microsatellite marker loci were not randomly distributed on chromosome 1D. Nineteen of the 24 (79.2%) microsatellite markers were mapped in the distal 30% genomic region of 1DS, whereas 25 of the 33 (75.8%) markers were assigned to the distal 59% region of 1DL. The powdery mildew resistance gene Pm24, originating from the Chinese wheat landrace Chiyacao, was previously mapped in the vicinity of the centromere on the short arm of chromosome 1D. A high density genetic map of chromosome 1D was constructed, consisting of 36 markers and Pm24, with a total map length of 292.7 cM. Twelve marker loci were found to be closely linked to Pm24. Pm24 was flanked by Xgwm789 (Xgwm603) and Xbarc229 with genetic distances of 2.4 and 3.6 cM, respectively, whereas a microsatellite marker Xgwm1291 co-segregated with Pm24. The microsatellite marker Xgwm1291 was assigned to the bin 1DS5-0.70-1.00 of the chromosome arm 1DS. It could be concluded that Pm24 is located in the ‘1S0.8 gene-rich region’, a highly recombinogenic region of wheat. The results presented here would provide a start point for the map-based cloning of Pm24.     

Assignment of the gene responsible for cystinuria (rBAT) and of markers D2S119 and D2S177 to 2p16 by fluorescence in situ hybridization

We have established rBAT (named as SLC3A1 in the Genome Data Base) as a gene responsible for cystinuria, a heritable disorder of amino acid transport. The cystinuria locus has been mapped by linkage between microsatellite markers D2S119 and D2S177. Fluorescene in situ hybridization (FISH) either with Alu-polymerasechain-reaction (PCR)-amplified sequences of a yeast artificial chromosome (YAC) containing the rBAT gene or with rBAT-specific PCR-amplified genomic fragments, and chromosome G-banding have cytogenetically mapped rBAT to 2p16.3. In order to correlate the physical and genetic information on cystinuria, we have performed FISH with combinations of Alu-PCR- amplified sequences from YACs containing rBAT or the D2S119 and D2S177 loci. In all cases, a fused signal is obtained that demonstrates their close physical location; this allows the assignment of rBAT, cystinuria and their linked markers, D2S119 and D2S177, to 2p16.     

A genetic linkage map for Eucalyptus globulus with candidate loci for wood,fibre, and floral traits

A genetic linkage map containing potential candidate loci for wood, fibre and floral traits has been constructed for Eucalyptus globulus (Labill.) based on the segregation of 249 codominant loci in an outbred F₁ population of 148 individuals. The map contains 204 RFLP loci, including 31 cambium-specific expressed sequence tags (ESTs) and 14 known function genes, and 40 microsatellite and five isozyme loci. Independent male and female maps were constructed, and the 98 loci (39%) that segregated in both parents were used to combine the parental maps into an integrated map. The 249 loci mapped to 11 major linkage groups (n=11 in eucalypts) and a 12th small linkage group containing three loci that segregated in the male parent only. Total map distance is 1375 cM with an average interval of 6 cM. Forty one of the mapped loci identify known proteins (five isozymes) or sequences with known function (14 genes and 22 ESTs). The mapped genes include enzymes involved in lignin and cell-wall polysaccharide biosynthesis, and floral-development genes. This map will be used to locate quantitative trait loci for wood, fibre, and other traits in Eucalyptus. Received: 30 August 2000 / Accepted: 23 March 2001     

Genetic analysis of resistance to Type-1 Diabetes in ALR/Lt mice,a NOD-related strain with defenses against autoimmune-mediated diabetogenic stress

ALR mice are closely related to type-1 diabetes mellitus (T1DM)-prone NOD mice. The ALR genome confers systemically elevated free radical defenses, dominantly protecting their pancreatic islets from free radical generating toxins, cytotoxic cytokines, and diabetogenic T cells. The ALR major histocompatibility complex (MHC) (H2^gx haplotype) is largely, but not completely identical with the NOD H2^g7 haplotype, sharing alleles from H2-K through the class II and distally into the class III region. This same H2^gx haplotype in the related CTS strain was linked to the Idd16 resistance locus. In the present study, ALR was outcrossed to NOD to fine map the Idd16 locus and establish chromosomal regions carrying other ALR non-MHC-linked resistance loci. To this end, 120 (NOD×ALR)×NOD backcross progeny females were monitored for T1DM and genetic linkage analysis was performed on all progeny using 88 markers covering all chromosomes. Glucosuria or end-stage insulitis developed in 32 females, while 88 remained both aglucosuria and insulitis free. Three ALR-derived resistance loci segregated. As expected, one mapped to Chromosome 17, with peak linkage mapping just proximal to H2-K. A novel resistance locus mapped to Chr 8. A pairwise scan for interactions detected a significant interaction between the loci on Chr 8 and Chr 17. On Chr 3, resistance segregated with a marker between previously described Idd loci and coinciding with an independently mapped locus conferring a suppressed superoxide burst by ALR neutrophils (Susp). These results indicate that the Idd16 resistance allele, defined originally by linkage to the H2^gx haplotype of CTS, is immediately proximal to H2-K. Two additional ALR-contributed resistance loci may be ALR-specific and contribute to this strain's ability to dissipate free-radical stress.     

Blood group association with severity and speed of the halothane reaction1

The second generation (n= 227) of British Landrace pigs from selected halothane-positive parents (36 litters) were blood-typed for the S(A-0), H and Phi loci and subjected to four 5-minute halothane tests at 21, 35, 49 and 63 days of age. Cumulative scores based on seventy and speed of reaction were analysed in relation to single-locus blood group genotypes and linkage group sequences at two and three loci. A highly significant negative correlation (r = -0.79) was found between severity and speed of reaction. Significant differences occurred between blood group genotypes and linkage groups in both severity and speed of reaction. Genotypes S s/s, H a/a or H a/- and Phi B/B and linkage groups involving these three types had the highest cumulative reaction score and the fastest reaction time, whereas genotypes Phi A/B, S S/S or S S/s and H a/cd and linkage groups with these types had the Iowest and slowest reaction scores. Some differences between genotypes and linkage groups were attributed to phenotypically halothane-positive parents and offspring being genotypically Hal N/n. These effects could result from linkage with heterozygous types such as H a/cd and S S/s. The possible role of the H ^cd allele acting as a genetic marker for a suppressor gene to the halothane reaction is discussed.     

Isozymic gene linkage map of the tomato: Applications in genetics and breeding

Summary New linkage data are presented for the situation of five previously unlocated isozymic loci of the tomato and closely related species with homosequential chromosomes.Prx-1 lies on chromosome 1, where it is also linked withSkdh-1; Aps-2 is linked withGot-4 on chromosome 8;Tpi-2 has been allocated to chromosome 4; and a linkage has been detected betweenPgi-1 andEst-4, whose respective chromosome has not yet been determined. These and previously published data have been summarized in the form of an isozyme linkage map. Twenty-two loci have thus been mapped on nine of the twelve tomato chromosomes. We discuss some new applications of mapped isozymic genes. In certain types of segregations, isozymic genes are far more efficient than morphological markers in providing linkage information. They greatly expedite the cytogenetic investigation of species hybrids and can be utilized to facilitate backcross transfers of genes from wild to cultivated taxa.