We report a bovine linkage map constructed with 1236 polymorphic DNA markers and 14 erythrocyte antigens and serum proteins. The 2990-cM map consists of a sex-specific, X chromosome linkage group and 29 sex-averaged, autosomal linkage groups with an average interval size of 2.5 cM. The map contains 627 new markers and 623 previously linked markers, providing a basis for integrating the four published bovine maps. Orientation and chromosomal assignment of all the linkage groups, except BTA20 and BTA22, was provided by 88 markers that were assigned previously to chromosomes. This map provides sufficient marker density for genomic scans of populations segregating quantitative trait loci (QTL) and subsequent implementation of marker-assisted selection (MAS) mating schemes.

A cattle genetic linkage map was constructed which covers more than 95 percent of the bovine genome at medium density. Seven hundred and forty six DNA polymorphisms were genotyped in cattle families which comprise 347 individuals in full sibling pedigrees. Seven hundred and three of the loci are linked to at least one other locus. All linkage groups are assigned to chromosomes, and all are orientated with regards to the centromere. There is little overall difference in the lengths of the bull and cow linkage maps although there are individual differences between maps of chromosomes. One hundred and sixty polymorphisms are in or near genes, and the resultant genome-wide comparative analyses indicate that while there is greater conservation of synteny between cattle and humans compared with mice, the conservation of gene order between cattle and humans is much less than would be expected from the conservation of synteny. This map provides a basis for high-resolution mapping of the bovine genome with physical resources such as Yeast and Bacterial Artificial Chromosomes as well as providing the underpinning for the interpolation of information from the Human Genome Project.

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We have independently isolated and characterized cDNA and genomic clones for the human coagulation factor IX. Sequence analysis in both cases indicates that threonine is encoded by the triplet ACT as the third residue of the activation peptide. This is in agreement with some earlier reports but in disagreement with others that show the alanine triplet GCT at this position. The discrepancy can thus be accounted for by natural variation of a single nucleotide in the normal population. Amino acid sequence analyses of activated factor IX from plasma samples of four individuals yielded two cases of alanine and two cases of threonine at the third position of the activation peptide. In factor IX from pooled plasma and in factor IX from a heterozygous individual, however, both alanine and threonine were found. Taken together, the findings show that a prevalent nondeleterious dimorphism exists in the activation peptide of human coagulation factor IX.Factor IX is the plasma protein that is missing or defective in individuals afflicted with the X-chromosome-linked bleeding disorder hemophilia B. Its role in the blood coagulation cascade is to activate factor X through interactions with calcium, membrane phospholipids, and factor VIII. Factor IX circulates as an inactive zymogen until proteolytic release of its "activation peptide" allows it to assume the conformation of an active serine protease.At the molecular level, it is known that hemophilia B may result from a variety of genetic changes (1, 2). Partial and/or complete deletions of the factor IX gene have been shown to be responsible for the disease in some cases (3,4). Several hemophilia B variants have also been described that show normal levels of the factor IX protein by immunological methods but have reduced or negligible activity in clotting assays. These variants have been designated CRM+ (crossreacting material positive). One of the CRM+ variants, factor IX Chapel Hill, results from an amino acid substitution at one of the proteolytic activation sites, blocking cleavage and subsequent activation (5). A change affecting the other cleavage site is likely to be involved in the variant factor IXDeventer (6).The molecular defect in another CRM+ variant, factor IXAlabama (7), is presently under study in our laboratories. The dimorphism described in this report, however, appears to be the result of a nondeleterious mutation which has been fixed in the normal population.As early as 1978, a partial amino acid sequence was reported for the amino-terminal region of the activation peptide of human factor IX (8). This analysis, apparently done on material from pooled plasma, showed an aminoterminal sequence Ala-Glu-Thr-Val-Phe-for the activation peptide, in agreement with a previously determined sequence for the corresponding region from bovine factor IX (9). No mention was made of alanine at the third position. Several years later, however, the same laboratory did report a cDNA sequence for human factor IX which indicated the presence of an alanine codon at the th...

Mitochondrial DNA was extracted from hepatic tissue of 50- and 300-day-old male BHE/cdb and Sprague-Dawley rats. The complete gene for the F0ATPase subunits 6 and 8 was sequenced. Four nucleotide substitutions were found: three of the substitutions were silent; the other substitution at position 523 was not. Its codon dictates the substitution of asparagine for aspartic acid in a critical location (in the polar pocket) of the F0ATPase. It is possible that this point mutation may explain previously reported decreases in ATP synthesis efficiency in BHE/cdb rats compared to Sprague-Dawley rats.