K. Bender

[Esterase D polymorphism: demonstration by high-voltage, starch-gel electrophoresis and presentation of allele frequencies (author's transl)].

SummaryEsterase D (Es D) isoenzymes were separated by means of high-voltage starchgel electrophoresis. The protein has a dimeric structure and is controlled by a single autosomally inherited gene locus with so far 3 detected alleles. The allele frequencies in 185 unrelated individuals from South West Germany are: Es D1=0.8892, Es D2=0.1081, Es D3=0.0027.ZusammenfassungEsterase D-Isoenzyme wurden mit Hilfe der Hochspannungsstärkegel-elektrophorese getrennt. Das Es D-Protein hat eine dimere Struktur und wird von einem autosomalen Genlocus mit bislang 3 entdeckten Allelen kontrolliert. Die Allelhäufigkeiten bei einer 185 Personen umfassenden südwestdeutschen Population betrugen: Es D1=0,8892, Es D2=0,1081, Es D3=0,0027.Esterase D-Isoenzyme wurden mit Hilfe der Hochspannungsstarkegel-elektrophorese getrennt. Das Es D-Protein hat eine dimere Struktur und wird von einem autosomalen Genlocus mit bislang 3 entdeckten Allelen kontrolliert. Die Allelhaufigkeiten bei einer 185 Personen umfassenden sudwestdeutschen Population betrugen: Es D1=0,8892, Es D2=0,1081, Es D3=0,0027.

Biochemical markers in inbred strains of the rat (Rattus norvegicus).

Klaus Bender 1, M a r k Adams 2, Peter R. Baverstock 2, Maria den Bieman 3, Siegbert Bissbort 1, Rad im Brdi~ka 4, Geoffrey W. Butcher 5, Dona ld V. Cramer 6, Otto yon Deimling 7, Michael F .W. Festing 8, Eberhard Gtinther 9, Rona ld D. G u t t m a n n 1°, Hans J. Hedrich 11, Philip B. Kendall 12, Reinhard Kluge i t , Ren6 Moutier 13, Babette Simon 7, James E. W o m a c k ~4, Junzo Yamada ~5, and Bert van Zutphen 3

Linkage data suggesting allelic heterogeneity for paramyotonia congenita and hyperkalemic periodic paralysis on chromosome 17

SummaryParamyotonia congenita (PC), an autosomal dominant non-progressive muscle disorder, is characterised by cold-induced stiffness followed by muscle weakness. The weakness is caused by a dysfunction of the sodium channel in muscle fibre. Parts of the gene coding for the α-subunit of the sodium channel of the adult human skeletal muscle (SCN4A) have been localised on chromosome 17. To investigate the role of this gene in the etiology of PC, a linkage analysis in 17 well-defined families was carried out. The results (z=20.61, Θ=0.001) show that the mutant gene responsible for the disorder is indeed tightly linked to the SCN4A gene. The mutation causing hyperkalemic periodic paralysis (HyperPP) with myotonia has previously been mapped to this gene locus by the same candidate gene approach. Thus, our data suggest that PC and HyperPP are caused by allelic mutations at a single locus on chromosome 17.

Haplotype analysis of the linkage group HLA-A:HLA-B:Bf and its bearing on the interpretation of the linkage disequilibrium

SummaryThe analysis of 650 HLA-A:HLA-B:Bf three-factor haplotypes revealed significant associations only between alleles of the very closely linked genes HLA-A and HLA-B, and HLA-B and Bf, respectively. Most striking is the highly significant association of the rare Bf variant F1 with HLA-B18 and of S1 with HLA-B13, HLA-B14, and HLA-Bw21. Only random allele distributions were observed when considering the somewhat more distant genes HLA-A and Bf or the higher order interaction at all three genes. From these findings it seems likely that the linkage disequilibrium within the MHC is not due to selective forces, but rather due to a short evolutionary period.

Human C4 polymorphism: Pedigree analysis of qualitative, quantiative, and functional parameters as a basis for phenotype interpretations

SummaryTen families with 82 members were investigated for C4A- and B polymorphism in a blind trial. Phenotyping was done on neuraminidase treated sera by immunofixation and simulataneously by hemolytic overlay electrophoresis. In addition Rg, Ch, BF, C2, HLA-A, B, C, DR, and GLO were determined. After decoding the samples the reliability of blind typing was found to be 84.4% according to segregation patters. Inconsistencies occurred mostly when A 4, A 2, or A 92 were present. The detection of silent A*Q0 and B*Q0 alleles was more critical than that of “difficult” allotypes. The quantitation of the C4A/B ratio by densitometry of stained gels or by conventional immunochemical measurements of serum C4 level could not substantially improve the identification of A*Q0 or B*Q0. C4 dependent activity in radial diffusion hemolysis showed satisfactory correspondence with the number of expressed C4B alleles. At least three haplotypes with two C4A genes (duplicated A genes) were observed as ascertained from offspring analysis in accordance with the MHC segregation pattern. Individuals with the duplicated C4A gene (C4A*3. A*2. in the absence of any other expressed A allele or together with C4A*92) showed only partial inhibition of Rodgers antisera. Partial inhibition of Chido antisera was seen in individuals with C4B 2 (in the absence of other B allotypes). The findings support the hypothesis of at least two structural C4 loci. The also demonstrate the inconsistency of quantitative data in the recognition of silent alleles.

Esterase. XXI. Es-9, a possibly new polymorphic esterase in Mus musculus genetically linked to Es-2

A so far undescribed gene controlling zone III esterases has been detected by means of disc gel electrophoresis of kidney homogenates from the two inbred mice strains NMRI and SK/Cam. The gene is tentatively designated Es-9, and the two codominant alleles are designated Es-9a and Es-9b. Es-9 esterases are present in many tissues, but, unlike the other zone III esterase (controlled by Es-5), are not found in the serum. Close linkage with the Es-2 gene leads us to map the Es-9 gene on chromosome 8.

Cytogenetic and biochemical differences between Apodemus sylvaticus and Apodemus flavicollis, possibly responsible for the failure to interbreed

Abstract 1. 1. In the two closely related rodent species, Apodemus sylvaticus and Apodemus flavicollis , thirty-three different protein markers and the chromosome banding pattern as produced by special staining techniques were compared. Breeding and interbreeding experiments were also performed. 2. 2. Both species differ in the electrophoretic position of twelve out of thirty-three protein markers and in the existence of telomeric heterochromatin on five chromosome pairs. 3. 3. Interspecific hybrids never occurred, neither within the population nor in the laboratory interbreeding experiments with or without hormonal pretreatment. This failure may be due to the genetic differences between both species.

Linkage relationships between retinoschisis, Xg, and a cloned DNA sequence from the distal short arm of the X chromosome

SummaryA cloned DNA sequence, RC8, from the short arm of the X chromosome which is linked to the Duchenne muscular dystrophy (DMD) gene has been employed to study linkage relationships with the Xg-linked retinoschisis (RS) locus. Results of three point linkage analyses in two families suggest that the gene order on Xp is Xg-RS-RC8. Moreover, it can be inferred from these data that the genetic distance between Xg and DMD is approximately 55 cM.

C4 AND HLA HAPLOTYPES ASSOCIATED WITH PARTIAL INHIBITION OF ANTI‐RG AND ANTI‐CH

Rg and Ch typing was performed, by serum inhibition, on 145 families that had been typed for HLA/C4/BF/C2 with a view to assessing partial inhibition (p.i.) of anti‐Rg/Ch and its haplotype associations. Rg p.i. was found predominatly with the C4A*3A*,2,B*QO homoduplicated C4 haplotype and BFF. The original type of Ch p.i. (Nordhagen et al., 1980) was closely associated with the allotype C4B 2, which also occasionally exhibited complete inhibition (c.i.), but this Ch p.i. was also found with the C4A*1,B*QO haplotype (Rittner et al., 1984a). The second type of Ch p.i. (Giles, 1984) was closely associated with the C4B 1 allotype most frequently in the haplotype C4A*6,B*1 but also with C4A*3,B*1. Both types of Ch p.i. are usually found with BF S. The present data indicate that the determinants of Rg and Ch are not directly related to any particular C4 allotype or extended haplotype.

Es-6, a further polymorphic esterase in the rat

A further polymorphic rat esterase with broad tissue expression and restricted substrate specificity is described and tentatively called Es-6. Inbred rat strains have either fixed allele Es-6F or fixed allele Es-6S. Es-6 is not linked to the established esterase cluster consisting of the eight esterase loci Es-1, Es-2, Es-3M, Es-4M, Es-4W, Es-5 (=Es-3W), Es-7, and Es-8 in LG V of the rat or to RT1, Gc, c, a, and h. Esterases with apparently identical biochemical and genetical characteristics are Es-17 of the mouse and Es-A4 of humans.