The CEPH consortium linkage map of human chromosome 1

This paper describes the Centre d'Etude du Polymorphisme Humain (CEPH) consortium linkage map of human chromosome 1. The map contains 101 loci defined by genotypes generated from CEPH family DNAs with 146 different contributions from 11 laboratories. A total of 58 loci are uniquely placed on the map with likelihood support of at least 1000:1. The map extends from loci in the terminal bands of both chromosome arms (locus D1Z2 in 1p36.3 and D1S68 in 1q44) and is anchored at the centromere by the D1Z5 alpha-satellite polymorphism. With the exception of a single locus, the remaining loci are arrayed on the fixed map in short intervals and their possible locations are indicated. Multipoint linkage analyses provided estimates that the male, female, and sex-averaged maps extend for 308, 478, and 390 cM, respectively. The sex-averaged map contains only four intervals greater than 15 cM, and the mean genetic distance between the 58 uniquely placed loci is 6.7 cM.     

The CEPH consortium linkage map of human chromosome 15q

The CEPH consortium map of chromosome 15q is presented. The map contains 41 loci defined by genotypes generated from CEPH family DNAs with 45 different probe and restriction enzyme combinations contributed by 10 laboratories. A total of 29 loci have been placed on the map with likelihood support of at least 1000:1. The map extends from 15q13 to 15q25-qter. Multipoint linkage analyses provided estimates that the male, female, and sex-averaged maps extend for 127, 190, and 158 cM, respectively. The largest interval is 21 cM and is between D15S37 and D15S74. The on-average locus spacing is 5.6 cM and the mean genetic distance between the 21 uniquely placed loci is 8 cM.     

Genetic linkage map of human chromosome 21

Two of the most common disorders affecting the human nervous system, Down syndrome and Alzheimer's disease, involve genes residing on human chromosome 21. A genetic linkage map of human chromosome 21 has been constructed using 13 anonymous DNA markers and cDNAs encoding the genes for superoxide dismutase 1 (SOD1) and the precursor of Alzheimer's amyloid beta peptide (APP). Segregation of restriction fragment length polymorphisms (RFLPs) for these genes and DNA markers was traced in a large Venezuelan kindred established as a "reference" pedigree for human linkage analysis. The 15 loci form a single linkage group spanning 81 cM on the long arm of chromosome 21, with a markedly increased frequency of recombination occurring toward the telomere. Consequently, 40% of the genetic length of the long arm corresponds to less than 10% of its cytogenetic length, represented by the terminal half of 21q22.3. Females displayed greater recombination than males throughout the linkage group, with the difference being most striking for markers just below the centromere. Definition of the linkage relationships for these chromosome 21 markers will help refine the map position of the familial Alzheimer's disease gene and facilitate investigation of the role of recombination in nondisjunction associated with Down syndrome.     

A primary genetic linkage map for human chromosome 12

A primary genetic map for human chromosome 12 has been constructed from data on 23 restriction fragment length polymorphic systems collected in 38 normal families with large sibships. Linkage analysis of the genotypic data has ordered 16 loci into a continuous genetic map of 111 cM in males and 258 cM in females. Although most of the genetic map reflects a higher rate of recombination in females relative to males, significantly more frequent recombination was observed in males than in females in intervals between loci on the distal portion of the short arm of the chromosome. The mapping data shown here will serve as a first step toward a high-resolution genetic map for human chromosome 12.     

Twenty loci form a continuous linkage map of markers for human chromosome 2

We have used a combination of 20 DNA markers and 1 protein electromorph, defining 20 loci, to construct a genetic linkage map of chromosome 2. These markers form a continuous linkage group of 306 cM in males and 529 cM in females. Female map distances varied from approximately twofold higher to equivalence from those of males across the map. Among the DNA markers are six well-distributed, highly polymorphic markers reflecting loci that contain a variable number of tandem repeats that will be highly efficient anchor points for the eventual application of this map to studies of human genetic disease.     

A genetic linkage map of markers for human chromosome 20

A continuous genetic linkage map with five polymorphic DNA markers, including one that defines a locus containing a variable number of tandem repeats (VNTR), has been constructed from genotypic analysis of 59 large reference families. The map spans a genetic distance of 105 cM in males and 115 cM in females and provides initial anchor points for a high-resolution map of human chromosome 20.     

A genetic linkage map of human chromosome 9q.

A genetic linkage map of human chromosome 9q, spanning a sex-equal distance of 125 cM, has been developed by genotyping 26 loci in the Venezuelan Reference Pedigree. The loci include 12 anonymous microsatellite markers reported by Kwiatkowski et al. (1992), several classical systems previously assigned to chromosome 9q, and polymorphisms for the genes tenacin (HXB), gelsolin (GSN), adenylate kinase 1 (AK1), arginosuccinate synthetase (ASS), ABL oncogene (ABL1), ABO blood group (ABO), and dopamine beta-hydroxylase (DBH). Only a marginally significant sex difference is found along the entire length of the map and results from one interval, between D9S58 and D9S59, that displays an excess of female recombination. A comparison of the genetic map to the existing physical data suggests that there is increased recombination in the 9q34 region with a recombination event occurring every 125-400 kb. This map should be useful in further characterizing the relationship between physical distance and genetic distance, as well as for genetic linkage studies of diseases that map to chromosome 9q, including multiple self-healing squamous epithelioma (MSSE), Gorlin syndrome (NBCCS), xeroderma pigmentosum (XPA), nail-patella syndrome (NPS1), torsion dystonia (DYT1), and tuberous sclerosis (TSC1).     

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.     

An extended genetic linkage map of markers for human chromosome 10

We have extended, in both directions, our recently published genetic map of markers for human chromosome 10 by the addition of 10 newly defined arbitrary loci. The map now covers 230 cM in males and 329 cM in females. In addition, three new markers, one of them a new RFLP at the IRBP gene locus, have been mapped in the vicinity of the locus responsible for multiple endocrine neoplasia type 2A (MEN2A). A significantly higher frequency of recombination in males than in females was observed near both ends of the new map.     

A comparative linkage and physical map of bovine chromosome 24 with human chromosome 18

Polymorphic microsatellites have been developed in the vicinity of nine genes on bovine chromosome (BTA) 24, all orthologous to genes on human chromosome (HSA) 18. The microsatellites have been isolated from bacterial and yeast artificial chromosome clones containing the genes. A linkage map was developed including these polymorphic markers and four anonymous, published microsatellites. Yeast artificial chromosomes containing six of these genes have also been mapped using fluorescent in situ hybridization (FISH), thereby tying the linkage map together with the physical map of BTA24. Comparing gene location on HSA18 and BTA24 identifies four regions of conserved gene order, each containing at least two genes. These genes identify six regions of conserved order between human and mouse, two more than in the human-bovine comparison. The breakpoints between regions of conserved order for human-bovine are also breakpoints in the human-mouse comparison. The centromere identifies a fifth conserved region if the BTA24 centromere is orthologous with the HSA18 centromere. Received: 17 September 1998 / Accepted: 4 December 1998     

Comprehensive linkage map of bovine chromosome 27

The results of genotypic data contributed to the International Society for Animal Genetics (ISAG) Bovine Chromosome 27 Workshop are presented. Eight laboratories contributed 23 261 informative meioses from 44 loci. Eighteen loci were typed by at least two laboratories and were used to construct a consensus linkage map. Twenty-one loci were subsequently incorporated into a comprehensive map. The sex-averaged consensus map covered 66.9 cM. The sex-averaged comprehensive map was 75.5 cM, while the female and male maps were 73.1 and 63.7 cM, respectively. Five loci were excluded from the analysis because of ambiguous position in the linkage group and a low LOD score (less than 2.0). Average distance between loci in the comprehensive map was 1.98 cM.     

Comprehensive linkage map of bovine chromosome 11

The results of genotypic data contributed to the International Society of Animal Genetics (ISAG) Bovine Chromosome 11 (BTA11) Workshop are presented. Six laboratories contributed a total of 26 199 informative meioses from 80 loci. Thirty-six loci were typed by at least two independent laboratories and were used to construct a consensus linkage map of the chromosome. The remaining loci were subsequently incorporated into a comprehensive map. The sex-averaged consensus map covered 128.9 cM. The female consensus map was 101.2 cM, while the male consensus map was 129.8 cM. The comprehensive sex-averaged map was 134.2 cM and the average genetic distance between loci was 1.72 cM.     

Twelve loci form a continuous linkage map for human chromosome 18

We have constructed a primary genetic map of human chromosome 18 consisting of 11 DNA markers and one serological marker (JK). Two of these loci define highly polymorphic VNTR systems. The markers define a continuous genetic linkage map of 97 cM in males and 205 cM in females; female genetic distances in a panel of 59 three-generation families were consistently about twice those observed in males. The high odds in support of the linear order of the markers on this recombination map, and the extent of coverage of chromosome 18, indicate that this map will permit efficient linkage studies of human genetic diseases that may be segregating on chromosome 18 and will provide anchor points for development of high-resolution maps for this chromosome.     

A genetic linkage map of 27 markers on human chromosome 21.

We have constructed a genetic linkage map of the long arm of human chromosome 21 comprising 27 DNA markers. This map is an updated version of that reported earlier by group (1989, Genomics 4: 579-591), which contained 17 DNA markers. The current markers consist of 10 genes and 17 anonymous sequences. Traditional methods (restriction fragment length polymorphisms) were used to map 25 of these markers, whereas 2 markers were studied by polymerase chain reaction amplification of (GT)n dinucleotide repeats. Linkage analysis was performed on 40 CEPH families using the computer program packages LINKAGE, CRI-MAP, and MAPMAKER. Recombination rates were significantly different between the sexes, with the male map being 132 cM and the female map being 161 cM, assuming Kosambi interference and a variable ratio of sex difference in recombination. Approximately one-half of the crossovers in either sex occur distally, in terminal band 21q22.3, which also contains 16 of the markers studied. The average distance between adjacent markers was 6 cM.     

Continuous linkage map of human chromosome 14 short tandem repeat polymorphisms.

Nine moderately to highly informative short tandem repeat polymorphisms were assigned to chromosome 14 using somatic cell hybrids and were mapped using linkage analysis. The nine markers formed a continuous linkage map covering almost the entire long arm from 14q11.2 to q32. The markers filled a large gap within previously reported linkage maps for this chromosome. Best order of the new loci from q11.2 to q32 was D14S50, D14S54, D14S49, D14S47, D14S52, D14S53, D14S55, D14S48, and D14S51. The order shown for all adjacent pairs of loci was very strongly favored with the exception of loci pair D14S55 and D14S48, for which the order was moderately favored. Map lengths for the nine loci were 142 cM in females and 72 cM in males. Female recombination frequencies exceeded male recombination frequencies in the middle and distal portions of the map.     

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 linkage map of distal mouse chromosome 12

To refine the linkage map of distal mouse Chromosome 12, we have identified DNA restriction fragment variants associated with a creatine kinase gene (Ck-3), the Akt proto-oncogene, an Abelson proviral integration site (D12N1), and the immunoglobulin heavy chain V_H3609 variable region family (Igh-V36). The patterns of inheritance of these markers in backcross progeny and recombinant inbred mouse strains allowed their localization with respect to previously mapped genes to yield the linkage map: Aat-15.8 cM-Ck-3-0.9 cM-(Crip, Akt, Igh-C)-0.3 cM-(D12N1, Igh-V). This map confirms genetically the localization of the Igh-V gene complex distal to Igh-C on the chromosome. It differs from previous maps in placing D12N1 distal to Igh-C, and in suggesting that the Igh-V gene complex spans less than one centiMorgan (cM).Other DNA sequence variants detected with the creatine kinase probe allowed definition of four additional genetic loci: Ck-1 near Lmyc-1 on Chromosome 4; Ck-2 between Upg-1 and Hprt-ps1 (D17Rp10) on distal Chromosome 17; Ck-4 near Mpmv-17 and Mls-3 on Chromosome 16; and Ck-5 near Hba on Chromosome 11.     

A multilocus linkage map of mouse chromosome 8

We present a genetic linkage map of mouse chromosome 8 that spans 53 cM and includes eight cloned loci. This map was derived from analysis of 100 progeny of an interspecific backcross between Mus spretus and Mus musculus domesticus. Genes that were mapped in this analysis include L7, Plat, Lpl, Ucp, Es, Mt-1, Um, and Tat. This analysis positions a new extremely proximal marker on chromosome 8, which is discussed as a potential candidate gene for the nervous locus. These linkage data will be useful for the mapping of additional loci on chromosome 8.     

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.