Genetic diversity among Canadienne, Brown Swiss, Holstein, and Jersey cattle of Canada based on 15 bovine microsatellite markers.

The genetic diversity among Canadienne, Brown Swiss, Holstein, and Jersey cattle was estimated from relationships determined by genotyping 20 distantly related animals in each breed for 15 microsatellites located on separate chromosomes. The Canadienne, Holstein, and Jersey cattle had an average of six alleles per loci compared with five alleles for Brown Swiss. Furthermore, a number of potentially breed-specific alleles were identified. The allele size variance among breeds was similar, but varied considerably among loci. All of the loci studied were equally heterozygous, as were Brown Swiss, Canadienne, and Holstein cattle (0.68-0.69) whereas Jersey cattle showed lower heterozygosity (0.59). The within-breed estimates of genetic distance were greater than zero and significant. The genetic distance between Canadienne and Holstein (0.156), Brown Swiss (0.243), and Jersey (0.235) was negligible, suggesting close relationship. Concurrently, Brown Swiss and Holstein (0.211) cattle also demonstrated close relationship. In contrast, the Jersey breed was genetically distant from the Brown Swiss and Holstein cattle (0.427 and 0.320, respectively). The characterization of Canadienne cattle, as part of the genetic resource conservation effort currently underway in Canada, underscores the difficulty in scientifically establishing unique breeds. Therefore, the need to consider all relevant morphological characteristics and production performance in combination with available cultural, historical, pedigree, and molecular information becomes relevant when identifying breeds for conservation.

Identification of an E689K substitution as the molecular basis of the human acid alpha-glucosidase type 4 allozyme (GAA*4).

We have identified the molecular basis of the GAA*4 allozyme as a G to A transition at nt2065 which predicts the substitution of glutamic acid by lysine at codon 689 (E689K). The conclusion that this change represents the molecular basis of the GAA*4 allozyme is based on 1) presence of the G2065A in homozygosity in a known GAA*4 homozygote, 2) transient expression studies showing normal enzyme activity expressed by cDNA containing the G2065A transition and 3) isoelectric focusing studies showing a more cathodal pattern for the expressed product as compared to the common GAA*1, analogous to the patterns seen in normal and known GAA*4 lymphoid cells.

Assignment of the gene(s) governing Froese and Swann blood group polymorphism to chromosome 17q.

BACKGROUND: The red cell antigens Fra and Swa were first described in 1978 and 1959, respectively. Despite the fact that these antigens are well defined serologically, information regarding the gene(s) controlling antigenic expression was not known. The present study represents a continued effort to establish the chromosomal location of human blood group genes by family linkage studies. STUDY DESIGN AND METHODS: DNA from members of kindreds segregating for FR and SW was isolated from whole blood and analyzed for restriction fragment length polymorphisms of SLC4A1 and D17S41. RESULTS: Lods for linkage between FR:SLC4A1 and SW:D17S41 were determined. Peak lods of 5.72 for the FR:SLC4A1 pair and of 3.01 for the SW:D17S41 pair were observed; there was no evidence of recombination between either pair. CONCLUSION: Lods for the FR:SLC4A1 and the SW:D17S41 pairs exceed the formal level required to establish linkage. (3.00) It was therefore concluded that the gene(s) governing Froese and Swann blood group polymorphism are located on the long arm of chromosome 17.

Identification of an uncommon haptoglobin type using DNA and protein analysis.

The inherited variations in haptoglobin phenotypes are attributed to the homozygous and heterozygous combinations of three common autosomal alleles: HP*1F, HP*1S and HP*2. HP*1F and HP*1S encode polypeptides that differ by two amino acids at positions 51 and 53. The formation of HP*2 is postulated to have resulted from a breakage and subsequent reunion event at non-homologous positions of two HP*1 alleles. The most common form of HP*2 is HP*2FS in which the 5' end of HP*2 resembles HP*1F and the 3' end resembles HP*1S. Homologous crossing over between HP*2 and either an HP*1F or HP*1S allele in HP*2/HP*1 heterozygotes can change the usual type of HP*2 to three other forms: HP*2SS, HP*2FF or HP*2SF. We describe a nuclear family in which the uncommon genotype HP*2SS is one parent caused initial confusion in assigning genotypes to the rest of the nuclear family. The data demonstrate the need for a cautious approach when deducing haptoglobin genotypes from molecular analysis alone.

The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26.

Human tissues have two distinct cholinesterase activities: acetylcholinesterase and butyrylcholinesterase. Acetylcholinesterase functions in the transmission of nerve impulses, whereas the physiological function of butyryl-cholinesterase remains unknown. An atypical form of butyrylcholinesterase or the absence of its activity leads to prolonged apnea following administration of the muscle relaxant suxamethonium. Inheritance of these butyrylcholinesterase variants is consistent with the enzyme activity being encoded in a single autosomal locus, BCHE (formerly CHE1 and E1), which has been assigned to chromosome 3. Previous in situ hybridization of a BCHE cDNA probe gave evidence of homologous sequences at 3q26 and 16q11-q23, raising the possibility of more than one locus coding for butyrylcholinesterase [H. Soreq, R. Zamir, D. Zevin-Sonkin, and H. Zakut (1987) Hum. Genet. 77: 325-328]. Using a different cDNA probe hybridized in situ to 46,XX,inv(3)(p25q21) metaphase chromosomes, we report here the localization of BCHE to a single autosomal location: 3q26.

Complementation by two non-homologous recombinant chromosomes 3.

The first example known to us of complementation by two non-homologous chromosomes 3 is present in the karyotype of a phenotypically normal brother of an inv(3)(p25q21) carrier. The normal chromosomes 3 are replaced by two complementary recombinant chromosomes 3. The longer recombinant duplicates 3q21-qter and is deficient for 3p25-pter. It is identical to the recombinant inherited by infants born with multiple congenital anomalies to inv(3)(p25q21) carriers. The shorter recombinant duplicates 3p25-pter and is deficient for 3q21-qter. This recombinant has previously been observed only in prometaphase spreads from sperm of an inv(3) carrier from the same kindred. Theoretically it is possible for the carrier of these complementary recombinant chromosomes 3 to produce sperm carrying either a normal 3, or the inversion 3, which could then fertilize an egg carrying a normal 3 followed by normal fetal development. However, the spouse of our propositus reported one first trimester spontaneous abortion, followed by no recognized pregnancy over the next 12 years of marriage.

The low-incidence red cell antigen Wra: genetic studies.

Studies of 91 individuals in three families allowed a genetic-linkage analysis of the gene governing the production of the low-incidence red cell antigen Wra and provided evidence that Wra is not a member of the Scianna, Landsteiner-Wiener, Chido/Rodgers, or XK blood group systems, and that the "WR" locus is excluded from autosomal sites or regions 1p34-p22.1, 1p21-q23, 1q32, 2p25, 3q21, 4q28-q32, 6p24-q12, 9q34.1-q34.2, 13q14.1-q14.2, 14q24.3-q32.1, 14q32.33, 16p13, 16q22.1, and 21q21-q22.1. "WR" is also excluded from within specified genetic distances of chromosomes 8 (GPT), 18 (JK), 19 (C3), 20 (ADA), and 22 (P1) loci, which brings its exclusion to approximately 10 percent (320cM) of the total genetic map of the genome. The possibility that "WR" is pseudoautosomal is deemed to be highly unlikely.

Localization of a locus for Charcot-Marie-Tooth neuropathy type Ia (CMT1A) to chromosome 17.

Phenotypic data for 71 genetic markers for members of five Caucasian kindreds were tested for linkage with the autosomal dominant mutations causing Charcot-Marie-Tooth (hereditary motor sensory) neuropathy type I, characterized by markedly reduced nerve conduction velocities. Lod score analysis gave no evidence of linkage to the closely linked chromosome 1 loci SPTA1-FY-F5-AT3 and APOA2. In contrast, these mutations were found to map closely (zeta = 10.828, theta = 0.0) to D17S58, an anonymous segment of DNA from 17p11.2-p11.1, and thus define the CMT1A locus. Segregation information data for an inferred recombinant offspring indicated that the CMT1A locus is probably proximal to MYH2, the locus encoding adult skeletal muscle myosin heavy polypeptide 2, which maps to 17p13. Analysis of the lod scores on a per kindred basis gave no evidence of genetic heterogeneity.

Evidence that SE is distal to LU on chromosome 19q.

Analysis of a family informative for chromosome 19 loci establishes that the Lutheran blood group locus (LU) lies between the third component of human complement (C3) and the secretor loci (SE). Previously published lod scores for C3:LU are increased from 2.94 to 3.80. The linkage relationships (zeta and theta) between C3, LU, and SE are examined, and the proposed order and approximate genetic distances are determined to be: pter--C3-10.6cM-cen-7.4cM-LU-9cM-SE--qter.

Exclusion of unassigned blood group system loci from the regulator of complement activation gene cluster on chromosome 1q32.

Genetic linkage analyses of the blood group system loci CO, DI, DO, KEL and YT in relation to F13B indicate that these loci are not members of the RCA gene cluster on chromosome 1q32. The data are presented to finalize the exclusion of the DAF carried red cell antigens from all of the 17 established blood group systems.