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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.

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 ( z = 10.828 , ĝq = 0.0) to D17S58, an anonymous segment of DNA from 17p11.2–p11.1, and thus define the CMT1A locus. Segragation 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.

The antithetical antigens YT1 and YT2 constitute the YT blood group system (International Society of Blood Transfusion system number 11). Despite being serologically well defined, the YT blood group locus (YT) has not secured a chromosomal location. In our report, peak lods of 3.61 at theta = 0.00 for YT:COL1A2 and of 3.31 at theta = 0.00 for YT:D7S13 allow us to assign YT to the long arm of chromosome 7.

The Waldner blood group antigen (WD1) was first recognized as a distinct erythrocyte surface structure in 1978. Occurring infrequently (incidence

The Diego blood group locus (DI) is tightly linked to the erythrocyte surface protein band 3 locus (EPB3) with z = 5.42 at theta = 0.00 for combined paternal and maternal meioses. Looser linkage between DI and D17S41 (z = 3.14 at theta = 0.09) for combined paternal and maternal meioses was also established. Taken together, these results indicate that the Diego blood group locus is located on the long arm of chromosome 17.

We have discovered a single homoallelic nucleotide substitution as the putative cause of the perinatal (lethal) form of hypophosphatasia in Canadian Mennonites. Previous linkage and haplotype analysis in this population suggested that a single mutational event was responsible for this autosomal recessive form of hypophosphatasia. The mutation is a guanosine-to-adenosine substitution at nucleotide position 1177 in exon 10 of the tissue nonspecific (liver/bone/kidney) alkaline phosphatase gene. This Gly317-->Asp mutation segregates exclusively with the heterozygote phenotype we previously assigned by biochemical testing (maximum combined lod score of 18.24 at theta = 0.00). This putative disease-causing mutation has not been described in controls nor in other non-Mennonite probands with both lethal and nonlethal forms of hypophosphatasia studied to date. This Gly317-->Asp mutation changes a polar glycine to an acidic aspartate at amino acid position 317 within the highly conserved active site region of the 507-amino-acid polypeptide. Carrier screening for this lethal mutation in our high-risk population is now feasible.

Familial lattice corneal dystrophy type I (LCD1) is a localized form of inherited amyloidosis limited to the corneal stroma. Recently the Finnish form of hereditary amyloidosis with lattice corneal dystrophy has been shown to be due to a mutation in the gelsolin gene (G654----A; Asp187----Asn). In this paper we exclude the gelsolin gene as the cause of the autosomal dominant form of isolated LCD1.

SUMMARY The Kell blood group locus (KEL) is tightly linked to the prolactin-inducible protein locus (PIP) with z=9.12 at o= 0.00 for combined paternal and maternal meioses. In view of the regional localization of PIP to 7q32-q36 (Myal et al. 1989a), a similar assignment for KEL is favoured.

Summary Odds favouring Do: PGD linkage (ž+ 3.56 at θ= 0.23) based on the average antilod are 920:20≃46:1. If Do is located on chromosome 1 it lies distal to PGD and recombination between PGD and Do occurs more frequently in male than in female meioses. Our data do not support Do:GC linkage.

Blood samples from a random series of Canadian Caucasians were phenotyped for 28 red cell enzyme systems and eight plasma protein systems. Polymorphism was found in 17 and rare variants in 11 of the systems. Allele frequencies are presented for these; distribution of phenotypes is in accordance with the Hardy–Weinberg equilibrium theory. In a complementary study of families there was no evidence of de novo mutation in any of the 36 systems and they allowed a minimum estimate of the frequency of null alleles in the ADA, C2, and GPT systems. Key words: polymorphism, red cell enzyme, plasma protein, phenotype, allele frequency, population.

No distortion was found when the genetics of esterase D (EC 3.1.1.1) in family data was examined for sex-phenotype ratio.

Linkage analysis of six nuclear families with infantile hypophosphatasia which were informative for the Rh blood group locus was performed. The maximum combined lod score was 4.76 with the recombinant distance (Θ) of 0.04. These preliminary data provide evidence for linkage between the genes for infantile hypophosphatasia and the Rh blood group and provisionally assign the gene locus for infantile hypophosphatasia (designated HOPS) to chromosome 1p.

Peak lods (zeta) of 3.48 at an estimated recombination fraction (theta) of 0.28 derived from 63 male and 90 female meioses indicate linkage between the KEL and YT blood group loci. Consideration is given to two families; a realistic interpretation of the data increases zeta to 4.24 at theta = 0.26.

The data establish linkage in both sexes for LDLR:LW (zeta = 8.43 at theta = 0.00) and in the male for LDLR:LU (zeta = 3.31 at theta = 0.00) and for LW:APOC2 (zeta = 3.90 at theta = 0.00). They confirm LDLR:C3 and APOC2:LU linkage in both sexes, and LW:LU linkage in the male. The loci constitute two tightly linked gene clusters, LDLR, C3, LW and APOC2, LU, SE, distinguished by measurable linkage in female meioses within but not between clusters. Argument is supported for a 19p13.2-cen position for LW and a long arm position for LU and SE.

A previously undescribed autosomal dominant syndrome has been observed in a large kindred with affected relatives spanning at least five generations. The phenotype is highly variable and appears to show complete penetrance. Affected persons have a progressively coarse, acromegaloid-like facial appearance and thickening of the lips and intraoral mucosa. The differences are discussed between this syndrome and three rather similar syndromes, pachydermoperiostosis, the Ascher syndrome, and multiple neuroma syndrome.

The results of the present study provide independent support for F13A:HLA linkage and refine the F13A:HLA and F13A:GLO1 linkage relationships. Analysis of the corresponding recombination fractions for the total paternal F13A:HLA and F13A:GLO1 peak lod scores (z) indicates a locus order of 6pter:F13A:HLA:GLO1:cen. Lod scores between F13A and PLG, a locus recently assigned to chromosome 6, exclude close linkage between these loci.