A genetic map of nine loci on bovine Chromosome 2

A male-specific genetic linkage map of nine loci on bovine Chromosome (Chr) 2 (BTA2) was constructed from 306 offspring belonging to six paternal halfsib families. Loci studied were the structural genes for liver/bone/kidney alkaline phosphatase (ALPL), Gardner-Rasheed feline sarcoma (v-fgr) oncogene homolog (FGR), alpha-L-fucosidase 1 (FUCA1), and fibronectin 1 (FN1), and the microsatellite loci ARO28, DU17S2, DU17S3, DU17S4, and DU17S5. Genotyping was performed by restriction fragment length polymorphism (RFLP) for structural genes and polymerase chain reaction (PCR) for the microsatellites. Two genetically independent linkage groups were identified. The order of genes in the first linkage group, L31, is (ARO28-FN1)-FGR-FUCA1-ALPL, covering a map distance of 34.1 cM between terminal markers. The second linkage group, L32, consists of DU17S2-DU17S5-DU17S4-DU17S3 and is 41.3 cM in length. Genetic linkage between FN1 and FGR confirms previous physical assignment of these genes to the same synteny group. Currently, the genetic linkage of FN1 and FGR is unique to cattle and thus localizes a site of chromosomal evolution to a 22-cM interval between the two loci.     

A genetic linkage map of 32 loci on human chromosome 10

We have constructed a genetic linkage map of human chromosome 10 based on DNA probes that detect 47 restriction fragment length polymorphisms (RFLPs) at 32 different loci. Segregation data were collected on a set of multigenerational families provided by the Centre d'Etude du Polymorphisme Humain and maps were constructed using recently developed multipoint analysis techniques. The length of the sex-averaged map is 178 cM and the sex-specific map lengths are 131 cM in males and 255 cM in females. Recombination is significantly higher in female meioses. The mean distance between loci is 5.6 cM for the sex-averaged map. The genetic map spans the length of the chromosome as judged by physical localization of probes by in situ hybridization techniques and mapping of the probes on human-hamster hybrid cell lines containing all or part of chromosome 10. The informativeness of two loci near the locus responsible for multiple endocrine neoplasia type 2A (MEN-2A) has been increased by isolation of cosmids that reveal additional RFLPs at these loci.     

A genetic and physical map of bovine chromosome 3

This paper reports a map of nine polymorphic microsatellite markers previously assigned to bovine chromosome 3 (BTA3) by somatic cell genetics. The linkage group covers 101 cM on the chromosome with an average intermarker distance of 13-9 cM. One marker (INRA200) was isolated from a peak of flow sorted chromosomes 2 and 3. Another marker (INRA197) was derived from a cosmid. The localization of the cosmid by in situ hybridization enabled the orientation of the linkage group on BTA3. Markers were relatively evenly spaced and consequently can be used to complement other mapping data about this chromosome. This establishes a framework of polymorphic markers that can be used to search for quantitative trait loci (QTL).     

A genetic linkage map of human chromosome 5 with 60 RFLP loci.

A genetic map of human chromosome 5 that contains 60 restriction fragment length polymorphism (RFLP) loci in one linkage group has been constructed. Segregation data using these markers and 40 large multigenerational families supplied by the Centre d'Etude du Polymorphisme Humain have been collected. Linkage analyses were performed with the program package CRI-MAP; using odds greater than 1000:1, 30 RFLP loci could be placed on the map. This genetic map spans 289 cM sex-equal, 353 cM in females, and 244 cM in males. While the relative rate of recombination for female meioses is nearly twice that of males over much of the chromosome, several instances of statistically significant excess male recombination were observed. The order of probes on the genetic map has been confirmed by their physical order as determined by somatic cell hybrid lines containing deletions of normal chromosome 5. There is concordance between the physical positions of markers and their genetic positions. Our most distal probes on the genetic map are cytologically localized to the most distal portions of the chromosome. This suggests that our genetic map spans most of chromosome 5.     

A genetic linkage map of 96 loci on the short arm of human chromosome 3.

We constructed a genetic map of 96 loci on the short arm of human chromosome 3 (3p) in 59 families provided by the Centre d'Etude du Polymorphisme Humaine (CEPH). Twenty-nine continuously linked loci were placed on the map with likelihood support of at least 1000:1; one locus, D3S213, was placed on the map with likelihood support of 871:1; D3Z1, an alpha satellite centromeric repeat probe, was placed on the map with likelihood support of 159:1; 65 loci were assigned regional locations. The average heterozygosity of the uniquely ordered markers was 49%. The map extends from 3p26, the terminal band of 3p, to the centromere (from D3S211 to D3Z1). Multipoint linkage analysis indicated that the male, female, and sex-averaged maps extend for 102, 147, and 116 cM, respectively. The mean genetic distance between uniquely ordered loci on the sex-averaged map was 4.0 cM. Probe density was greatest for the region of 3p between D3F15S2e and the telomere. The sex-averaged map contained two intervals greater than 10 cM. Seventeen probes were localized by fluorescence in situ hybridization. The loci described in this report will be useful in building an integrated genetic and physical map of this chromosome.     

A map of 22 loci on human chromosome 22.

We constructed a genetic linkage map of the entire long arm of human chromosome 22 with 30 polymorphic markers, defining 22 loci. The map consists of a continuous linkage group 110 cM long, when male and female recombination fractions are combined; average distance between the loci is 5.2 cM. All loci were placed on the map with high support against alternative orders (odds in excess of 1000:1). The order of loci presented in our map is in full agreement with that of the previous linkage maps of chromosome 22 and with the physical assignment of markers. Two markers included in this map, KI-831 (D22S212) and pEFZ31 (D22S32), allowed us to better define the region of the (11;22) translocation breakpoint specific for Ewing sarcoma. Ten additional polymorphic markers were placed on the 22-loci map with odds lower than 1000:1 against alternative locations. In total, we have introduced 29 new markers on the linkage map of chromosome 22.     

High-resolution genetic map of bovine chromosome 29 through focused marker development

Chromosome-specific libraries aid in the development of genetic maps and focus marker development in areas of the genome with identified quantitative trait loci (QTL). A small-insert BTA29 library constructed by microdissection of a 1:29 Rb-fusion cell line, was screened for dinucleotide repeats (CA)(15) and/or (GA)(15) with the goal of generating new genetic markers for this, the smallest bovine autosome. A total of 90 primer pairs were designed and 82 of these successfully amplified bovine genomic DNA by PCR. In addition to these 82 loci, primer pairs were developed for nine putative genes identified from the sequenced clones by BLAST searches of GenBank. A somatic cell panel was used to test for synteny of the new loci with two previously mapped BTA29 markers located on the MARC bovine linkage map. A total of 75 of the 82 microsatellite (ms) loci were integrated into the MARC bovine linkage map. Linkage analysis placed 69 ms markers on BTA29, five on BTAX and one on BTA1. Combined results of the somatic cell and linkage analyses place 79 new markers (ms and gene-related) on BTA29, six loci on BTAX and two loci on BTA1. The results of this effort significantly increase the marker density on BTA29, expanding the ability to fine map QTL associated with this chromosome.     

A genetic linkage map of chromosome 17

We have developed a genetic linkage map of 19 markers (including nine genes) on human chromosome 17, providing 13 reference points along virtually the entire length of this chromosome. The map covers an estimated 149 cM in length (sex-averaged), with a total length of 214 cM in females and 95 cM in males. This sex difference appears to be significant along virtually the entire length of the map. This map will be useful both for providing reference points for fine structure genetic and physical mapping and for genetic linkage studies of diseases, including von Recklinghausen neurofibromatosis and Charcot-Marie-Tooth disease.     

A radiation hybrid map of bovine chromosome one

Radiation hybrid (RH) mapping has proven to be an extremely powerful approach to constructing high density maps of human chromosomes and is experiencing increased use in other animals, including cattle. A 5000 rad bovine whole-genome radiation hybrid panel was recently constructed in order to integrate existing cattle linkage maps with evolutionarily conserved genes and provide high resolution comparative maps relative to humans and mice. We utilized this panel to construct a 19 marker framework map of bovine chromosome 1 (BTA1), which included 8 Type I loci and 11 Type II loci ordered with at least 1000:1 odds. A 35 marker comprehensive map including 15 Type I loci and 20 Type II loci was also produced. Of the 15 Type I loci ordered on the comprehensive map, three are ordered on HSA3 and five are ordered in three blocks on HSA21 on the human cytogenetic maps.     

A 2-cM genetic linkage map of human chromosome 7p that includes 47 loci.

A new high-resolution genetic linkage map for human chromosome 7p has been constructed. The map is composed of 47 loci (54 polymorphic systems), 19 of which are uniquely placed with odds of at least 1000:1. Four genes are represented, including glucokinase (GCK, ATP:D-hexose-6-phosphotransferase, EC 2.7.1.2) which was mapped via a (CA)n dinucleotide repeat polymorphism. The sex-average map measures 94.4 cM and the male and female maps measure 73.2 and 116.1 cM, respectively. We believe that the genetic map extends nearly the full length of the short arm of chromosome 7 since a centromere marker has been incorporated, and the most distal marker, D7S21, has been cytogenetically localized by in situ hybridization to 7p22-pter. The average marker spacing is 2 cM, and the largest interval between uniquely placed markers is 13 cM (sex-average map). Overall, female recombination was observed to be about 1.5 times that of males, and a statistically significant sex-specific recombination frequency was found for a single interval. The map is based on genotypic data gathered from 40 CEPH reference pedigrees and was constructed using the CRI-MAP program package. The map presented here represents a combined and substantially expanded dataset compared to previously published chromosome 7 maps, and it will serve as a "baseline" genetic map that should prove useful for future efforts to develop a 1-cM map and for construction of a contiguous clone-based physical map for this chromosome.     

A genetic map of human chromosome 17p

A genetic linkage map was constructed with 18 loci from the short arm and pericentric region of chromosome 17 typed on the CEPH reference families. The genetic map includes three markers extracted from the CEPH public database. Nine loci could be ordered using a threshold of odds of at least 1000:1 against alternative orders during the map construction process. With a reduced tolerance of 100:1, a total of 13 loci could be placed on the map spanning a distance of approximately 60 cM in females and 46 cM in males. There were statistically significant differences between the male and the female genetic maps. The order inferred from the genetic data was consistent with the physical localizations of these probes obtained from somatic cell hybrids and tumor deletion studies. This map should be useful for genetic fine mapping of 17p loci.     

A high-resolution comparative RH map of the proximal part of bovine chromosome 1

Current comparative maps between human chromosome 21 and the proximal part of cattle chromosome 1 are insufficient to define chromosomal rearrangements because of the low density of mapped genes in the bovine genome. The recently completed sequence of human chromosome 21 facilitates the detailed comparative analysis of corresponding segments on BTA1. In this study eight bovine bacterial artificial chromosome (BAC) clones containing bovine orthologues of human chromosome 21 genes, i.e. GRIK1, CLDN8, TIAM1, HUNK, SYNJ1, OLIG2, IL10RB, and KCNE2 were physically assigned by fluorescence in situ hybridization (FISH) to BTA1q12.1-q12.2. Sequence tagged site (STS) markers derived from these clones were mapped on the 3000 rad Roslin/Cambridge bovine radiation hybrid (RH) panel. In addition to these eight novel markers, 17 known markers from previously published BTA1 linkage or RH maps were also mapped on the Roslin/Cambridge bovine RH panel resulting in an integrated map with 25 markers of 355.4 cR(3000) length. The human-cattle genome comparison revealed the existence of three chromosomal breakpoints and two probable inversions in this region.     

A genetic map of mouse chromosome 1 near the Lsh-Ity-Bcg disease resistance locus

Isozyme and restriction fragment length polymorphism (RFLP) analyses of backcross progeny, recombinant inbred strains, and congenic strains of mice positioned eight genetic markers with respect to the Lsh-Ity-Bcg disease resistance locus. Allelic isoforms of Idh-1 and Pep-3 and RFLPs detected by Southern hybridization for Myl-1, Cryg, Vil, Achrg, bcl-2, and Ren-1,2, between BALB/cAnPt and DBA/2NPt mice, were utilized to examine the cosegregation of these markers with the Lsh-Ity-Bcg resistance phenotype in 103 backcross progeny. An additional 47 backcross progeny from a cross between C57BL/10ScSn and B10.L-Lshr/s mice were examined for the cosegregation of Myl-1 and Vil RFLPs with Lsh phenotypic differences. Similarly, BXD recombinant inbred strains were typed for RFLPs upon hybridization with Vil and Achrg. Recombination frequencies generated in the different test systems were statistically similar, and villin (Vil) was identified as the molecular marker closest (1.7 +/- 0.8 cM) to the Lsh-Ity-Bcg locus. Two other DNA sequences, nebulin (Neb) and an anonymous DNA fragment (D2S3), which map to a region of human chromosome 2q that is homologous to proximal mouse chromosome 1, were not closely linked to the Lsh-Ity-Bcg locus. This multipoint linkage analysis of chromosome 1 surrounding the Lsh-Ity-Bcg locus provides a basis for the eventual isolation of the disease gene.     

A molecular genetic linkage map of mouse chromosome 2

Interspecific backcross mice were used to create a molecular genetic linkage map of chromosome 2. Genomic DNAs from N2 progeny were subjected to Southern blot analysis using molecular probes that identified the Abl, Acra, Ass, C5, Cas-1, Fshb, Gcg, Hox-5.1, Jgf-1, Kras-3, Ltk, Pax-1, Prn-p, and Spna-2 loci; these loci were added to the 11 loci previously mapped to the distal region of chromosome 2 in the same interspecific backcross to generate a composite multilocus linkage map. Several loci mapped near, and may be the same as, known mutations. Comparisons between the mouse and the human genomes indicate that mouse chromosome 2 contains regions homologous to at least six human chromosomes. Mouse models for human diseases are discussed.     

A multipoint genetic linkage map of mouse chromosome 18

We have mapped 13 loci on mouse Chromosome 18 by Southern blot analysis of restriction fragment length polymorphisms among progeny from an interspecific backcross: (C57BL/6J X Mus spretus) X M. spretus. Complete haplotype analysis of 136 of these progeny was used to establish gene order and estimate genetic distances between loci. The gene order (from centromere to telomere) and recombination distances (in centimorgans) were as follows: PGK-1rs5-4.3-Tpi-10-11.8-(Egr-1, Hmg17-rs9)-2.1-Fgfa-2.2-Grl-1-10.1-(Cdx-1, Csfmr, Pdgfrb, Pdea, Rps14)-2.1-Adrb-2-22.9-Mbp. Pgk-1rs5, Tpi-10, Hmg17-rs9, and Rps14 had not been previously mapped in the mouse; Egr-1 had only been syntenically assigned to mouse Chr 18. Nine of the loci, spanning 18 cM, have homologs on the distal long arm of human Chr5--a region rich in genes encoding growth factors and receptors. An additional previously unmapped gene, Drd-1, predicted to be on mouse Chr 18 based on its human chromosomal location, was mapped to the middle region of mouse Chr 13.     

A molecular genetic linkage map of mouse chromosome 7

The homology between mouse chromosome 7 and human chromosomes 11, 15, and 19 was examined using interspecific backcross animals derived from mating C3H/HeJ-gld/gld and Mus spretus mice. In an earlier study, we reported on the linkage relationships of 16 loci on mouse chromosome 7 and the homologous relationship between this chromosome and the myotonic dystrophy gene region on human chromosome 19. Segregation analyses were used to extend the gene linkage relationships on mouse chromosome 7 by an additional 21 loci. Seven of these genes (Cyp2a, D19F11S1h, Myod-1, Otf-2, Rnu1p70, Rnu2pa, and Xrcc-1) were previously unmapped in the mouse. Several potential mouse chromosome 7 genes (Mel, Hkr-1, Icam-1, Pvs) did not segregate with chromosome 7 markers, and provisional chromosomal assignments were made. This study establishes a detailed molecular genetic linkage map of mouse chromosome 7 that will be useful as a framework for determining linkage relationships of additional molecular markers and for identifying homologous disease genes in mice and humans.     

A primary genetic map of chromosome 13q.

We have constructed a primary genetic map spanning most of human chromosome 13. A total of 14 polymorphic DNA sequences and one protein polymorphism provided, after construction of haplotypes, seven markers for the long arm of this chromosome. A panel of cell lines from 30 three-generation families with large sibship size served as the sample set. Pairwise cross analysis of the inheritance patterns of the marker loci established that six of the seven loci constituted a single linkage group; the seventh was localized by physical means. Significantly higher recombination rates were found in female than in male meioses in several intervals. The six closely linked loci were arranged, based on the two-point data, in three clusters, and a number of alternate gene orders were excluded by three-point linkage tests. The order and spacing of the individual loci were refined by linkage analyses that considered five loci jointly.     

A genetic linkage map of 27 loci from PND to FY on the short arm of human chromosome I.

A genetic linkage map of 27 loci on the short arm of human chromosome 1 has been developed by analysis of the 40 families in the Centre d'Etude du Polymorphisme Humain (CEPH) reference panel. Probes that recognize 14 novel RFLPs at loci designated D1S9-D1S22 were isolated from a flow-sorted chromosome 1 library. A linkage map of chromosome 1p was constructed from the genotypic data at these 14 loci, RFLPs at eight cloned genes (PND, ALPL, FUCA1, SRC2, MYCL, GLUT, TSHB, and NGFB), two previously identified RFLPs (D1S2 and D1S57), two blood group antigens (RH and FY), and the isozyme PGM1. All 27 loci form a continuous linkage group, from FY to PND, of 102 cM in males and 230 cM in females. This map provides a basis for highly informative multipoint mapping studies for most of the short arm of chromosome 1.     

A genetic linkage map of 17 markers on human chromosome 21

We have constructed a genetic linkage map of 17 markers on the long arm of human chromosome 21, including six genes and two anonymous loci with a variable number of tandem repeats. The estimated length of the map is 103 cM in males and 140 cM in females, assuming Kosambi interference. Recombination in females was approximately twice that in males between proximal markers. However, over half of the recombination events in either sex occur distally, in 21q22.3, although this region accounts for only about 15% of the physical length of chromosome 21.