The gene for coagulation factor XIII a subunit (F13A) is distal to HLA on chromosome 6

Summary The locus coding for the A subunit of coagulation factor XIII (F13A) is strongly linked with the major histocompatibility complex on chromosome 6. The maximum lod score was obtained at recombination fractions of 0.12 in males and 0.40 in females. The data suggest that the F13A locus is distal to HLA, probably within the 6p22 region.     

The structural gene for human coagulation factor X is located on chromosome 13q34

The gene coding for coagulation factor X was studied in a family segregating chromosomal abnormalities involving chromosomes 13 and 6. An individual monosomic for 13q34 was deficient in levels of clotting factors VII and X, while her brother, who is trisomic for 13q34, had elevated levels. DNA dosage studies with a cloned human factor X gene demonstrated that the low levels of factor X expression in the individual with the chromosome 13q34 deletion were due to the absence of one copy of the factor X structural gene. This confirms the assignment of the human gene coding for factor X to 13q34.     

Localization of the coagulation factor XIII A subunit gene (F13A) to chromosome bands 6p24----p25

Electrophoretic studies of the genetic variation of the A subunit of coagulation factor XIII (F13A) have shown that the A subunits expressed in placenta and in the circulation are the products of the same gene locus. In situ hybridization studies with a cDNA fragment encoding the amino terminal region of the A subunit have localized the gene to bands p24----p25 on chromosome 6. This confirms previous studies that showed linkage between F13A and the major histocompatibility complex.     

Linkage between the loci for mitochondrial malic enzyme (ME2) and coagulation factor XIIIA subunit (F13A)

Summary The locus for the mitochondrial malic enzyme (ME2) seems to be closely linked to the gene coding for the A subunit of coagulation factor XIII (F13A). From 18 informative families with 54 children a maximum lod score of 4.33 was obtained at a recombination fraction of 0.10. Since the assignment of F13A to the short arm of chromosome 6 was recently confirmed, the locus for ME2 can be added to this linkage group. The map order seems to be: GLO1-HLA-F13A-ME2.     

Extensive DNA polymorphism at the factor XIIIa (F13A) locus and linkage to HLA.

A 1,161-bp EcoRI fragment from the 5' end of the cDNA coding for human factor XIIIa (gene symbol F13A) was used to identify RFLPs in human DNAs. Several different RFLPs were identified with 15 different restriction enzymes. Two RFLPs detected with the restriction enzyme BamHI and one multiallelic RFLP detected with BclI were used for further studies. Linkage relationships between these three polymorphisms and the HLA complex were studied in DNA samples from the 40 Centre d'Etude du Polymorphisme Humain families. Combining all of the data to form highly informative haplotypes, we found linkage to HLA with a maximum lod score of 11.44 at a recombination fraction of .25 for males and .35 for females. These three RFLPs at the FXIIIa locus provide a highly informative marker for the short arm of chromosome 6 with an observed heterozygosity of 91%. Using this marker and the HLA locus, one can confirm or exclude the assignment of gene loci to most of chromosome 6p.     

Factor XI gene (F11) is located on the distal end of the long arm of human chromosome 4

Chromosomal localization of the gene for human coagulation factor XI (F11) was determined by in situ hybridization using a genomic DNA probe which contained exons VIII, IX, and X of the gene. The results indicate that the gene is located at 4q35.     

The locus for apolipoprotein E (apoE) is linked to the complement component C3 (C3) locus on chromosome 19 in man

Summary By two-dimensional electrophoresis of human serum a genetically determined polymorphism of apolipoprotein E (apoE) can be demonstrated. Three alleles occur with appreciable frequency in Caucasian populations. In the present study the segregation of apoE and complement component C3 (C3) types in material from Norwegian families has been studied. Linkage has convincingly been demonstrated between the two loci with a lod score of 3.00 in males at a recombination fraction of 13%. As it is known that the C3 locus is situated on chromosome 19 in man, apoE can be located to this specific chromosome. Positive linkage data do not, to our knowledge, at present exist with regard to other apolipoproteins.     

Tardy feathering locus (t) located on chromosome 1 in the chicken

The locus for tardy feathering (t), a recessive autosomal rate of feathering mutation, had been previously suggested to be on chromosome 1 in the chicken. Tests using both pea comb (P) and the breakpoint (B) of a chromosome translocation involving chromosome 1 (MN t(Z;l] verify that t lies on the long arm of chromosome 1, and shows linkage of 41.7 +/- 2.2 map units, with P located on the short arm.     

A major susceptibility locus for specific language impairment is located on 13q21

Children who fail to develop language normally-in the absence of explanatory factors such as neurological disorders, hearing impairment, or lack of adequate opportunity-are clinically described as having specific language impairment (SLI). SLI has a prevalence of approximately 7% in children entering school and is associated with later difficulties in learning to read. Research indicates that genetic factors are important in the etiology of SLI. Studies have consistently demonstrated that SLI aggregates in families. Increased monozygotic versus dizygotic twin concordance rates indicate that heredity, not just shared environment, is the cause of the familial clustering. We have collected five pedigrees of Celtic ancestry that segregate SLI, and we have conducted genomewide categorical linkage analysis, using model-based LOD score techniques. Analysis was conducted under both dominant and recessive models by use of three phenotypic classifications: clinical diagnosis, language impairment (spoken language quotient <85) and reading discrepancy (nonverbal IQ minus non-word reading >15). Chromosome 13 yielded a maximum multipoint LOD score of 3.92 under the recessive reading discrepancy model. Simulation to correct for multiple models and multiple phenotypes indicated that the genomewide empirical P value is <.01. As an alternative measure, we also computed the posterior probability of linkage (PPL), obtaining a PPL of 53% in the same region. One other genomic region yielded suggestive results on chromosome 2 (multipoint LOD score 2.86, genomic P value <.06 under the recessive language impairment model). Our findings underscore the utility of traditional LOD-score-based methods in finding genes for complex diseases, specifically, SLI.     

The Bf locus in the HLA region of chromosome 6: linkage and association studies.

Bf allele frequencies in a material of 172 unrelated Norwegians are given. Bf/HLA linkage relations in 49 informative matings with 178 children, and Bf/HLA association data of a material of 212 Bf-HLA haplotypes are presented. Of 171 informative meioses, there were no Bf-HLA-B recombinations, while 3 out of 158 Bf-HLA-A informative meioses showed recombination. There is significant association between the BfF and the HLA-BW35 allele. It is concluded that the Bf locus is situated on the HLA-B side of HLA-A within the HLA region, in very close proximity to HLA-B.     

A novel locus for autosomal dominant nonsyndromic hearing loss, DFNA13, maps to chromosome 6p.

Nonsyndromic hearing loss (NSHL) is the most common type of hearing impairment in the elderly. Environmental and hereditary factors play an etiologic role, although the relative contribution of each is unknown. To date, 39 NSHL genes have been localized. Twelve produce autosomal dominant hearing loss, most frequently postlingual in onset and progressive in nature. We have ascertained a large, multigenerational family in which a gene for autosomal dominant NSHL is segregating. Affected individuals experience progressive hearing loss beginning in the 2d-4th decades, eventually making the use of amplification mandatory. A novel locus, DFNA13, was identified on chromosome 6p; the disease gene maps to a 4-cM interval flanked by D6S1663 and D6S1691, with a maximum two-point LOD score of 6.409 at D6S299.     

The locus for apolipoprotein CII is closely linked to the apolipoprotein E locus on chromosome 19 in man

Summary We have demonstrated close linkage between the genes for apolipoprotein E (apoE) and apolipoprotein CII (apoCII). Families segregating for apoE protein variants were screened for a DNA restriction fragment length polymorphism close to the apoCII gene by using an apoCII cDNA clone. The maximum lod score is 4.52 (sexes combined) at a recombination frequency of zero. Given linkage, it may be assumed that no recombinations have happened in altogether 33 observed meioses. It is therefore evident that the apoCII gene is situated on chromosome 19, close to the apoE gene.     

Mapping of the human gene for epidermal growth factor receptor (EGFR) on the p13 leads to q22 region of chromosome 7

We previously reported that the structural gene for epidermal growth factor receptor (EGFR) can be mapped to the p22 leads to qter region of human chromosome 7 (Shimizu et al., 1979, 1980). In the present study, we produced two series of human-mouse cell hybrids by fusing mouse A9 cells that are deficient in EGFR with the human diploid fibroblast lines GM1356, 46,XX,t(1;7)(p34;p13), and GM2068, 46,XX,t(6;7)(q27;q22), both of which possess EGF receptors. Expression of EGF binding ability in the former series of cell hybrids was correlated with the retention of the human translocation chromosome containing the 7p13 leads to qter region, and in the latter series of cell hybrid it was correlated with the retention of the human translocation chromosome containing the 7pter leads to q22 region. Therefore, the EGFR gene can be localized in the p13 leads to q22 region of chromosome 7.