A genome-wide scan was performed, using nonparametric linkage analyses, to find susceptibility loci for type 2 diabetes mellitus in the Dutch population. We studied 178 families from The Netherlands, who constituted 312 affected sibling pairs. The first stage of the genome scan consisted of 270 DNA markers, with an average intermarker spacing of 13 cM. Because obesity and type 2 diabetes mellitus are interrelated, the data set was stratified for the subphenotype body mass index, corrected for age and gender. This resulted in a suggestive maximum multipoint LOD score of 2.3 (single-point P value, 9.7 x 10(-4); genome-wide P value, 0.028) for the most obese 20% pedigrees of the data set, between marker loci D18S471 and D18S843. In the lowest 80% obese pedigrees, two interesting loci on chromosome 2 and 19 were found, with LOD scores of 1.5 and 1.3. We provide independent evidence that the chromosome 18p11 locus, reported earlier from a Finnish/Swedish population, is of definite interest for type 2 diabetes mellitus in connection with obesity. Subsequently, our results indicate that two novel loci may reside on chromosomes 2 and 19, with minor effects involved in the development of type 2 diabetes mellitus in the Dutch population.

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In man-Chinese hamster somatic cell hybrids the segregation of the loci for 27 human enzyme markers and the species-specific surface antigens, including the HL-A histocompatibility antigens, was studied. The results show a synteny of the human loci for phosphoglucomutase 3, cytoplasmic malic enzyme, tetrameric indophenol oxidase, and HL-A. Furthermore, evidence is presented that the loci for the human species-specific antigens are distributed over several chromosomes.Human chromosomes are lost preferentially in man-rodent somatic cell hybrids. The study of these hybrids has considerably facilitated the analysis of gene linkage in man (1). Two or more human markers are located on the same chromosome (syntenic) when they are present or absent simultaneously in hybrid cell populations. M\ost of the known human syntenic groups detected via the analysis of hybrid cells are connected with loci coding for enzymes, since most of the homologous enzymes of man and rodent origin can be distinguished by means of electrophoretic techniques. Besides enzymes, antigens of both parental genomes are expressed in the hybrid cells (2). The genes coding for antigens are therefore another class of markers which can be used in synteny studies, as has been shown by Puck (3).In the present investigation the segregation patterns of 27 loci coding for human enzymes were studied and related to the expression of human species-specific surface antigens in manChinese hamster somatic cell hybrids. Furthermore, we examined whether the human locus for HL-A was segregating in close association with the locus for phosphoglucomutase 3 (PGM3, EC 2.7.5.1) in these hybrid cells, since family studies have suggested that these loci are linked (4, 5). MATERIALS AND METHODSHybrid somatic cell lines were obtained by fusion of mutant cell lines derived from the Chinese hamster DON cell line with normal or hypoxanthine-guanine phosphoribosyltransAbbreviations: HL-A, human histocompatibility antigens; PGM3, phosphoglucomutase 3; ME,, cytoplasmic malic enzyme; IPO-B, tetrameric indophenol oxidase; Ra/HeLa, rabbit antiserum against HeLa cells; ALS, horse anti-human lymphocyte serum; Hex-B, hexosaminidase B.

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