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The allele frequency distributions of three STR loci amplified by PCR have been studied in four Israeli communities: Ashkenazi Jews and three non-Ashkenazi groups, namely Moroccan, Yemenite, and Ethiopian Jews. The loci analyzed were CSF1PO, TPOX, and HUMTHO1. The typing was performed in sequencing polyacrylamide gels under denaturing conditions that could separate alleles with differences of a single base. The population data were analyzed with respect to Hardy-Weinberg (H-W) equilibrium and found that all loci meet the H-W expectations. No-ticeable differences were encountered between the four Jewish ethnic groups studied hereby indicating the importance of establishing a local database to be used in human identity testing in these different Israeli Jewish groups.

The Jewish population in Israel comprises of inhabitants of heterogeneous ethnic backgrounds. Genetic studies classify the Israeli Jewish population into two major groups: Ashkenazi from Central and Eastern Europe and Sephardic or non Ashkenazi, from the Mediterranean and North Africa. The present study was aimed at elucidating the differential influx of HLA class II alleles in Ashkenazi, in various non-Ashkenazi subgroups and in Israeli Moslem Arabs. Using the PCR-SSOP technique, a large number of alleles were detected at each of the loci examined (DRB1, DQA1 and DQB1). In addition, gene frequencies, characteristic DR/DQ linkage disequilibria, population distance and their corresponding dendogram, were used to study the relationship between Israelis as a group, non Jewish Caucasians and Blacks. These populations could be grouped into three main clusters: the first consists of all the Israeli groups with the exception of the Ethiopian Jews; the second consists of non Jewish Caucasians, with a clear distinction seen between Israelis and non Jewish Europeans and U.S. Caucasians; the third, composed of Blacks, is distinctly different from the other populations. Ethiopian Jews were found to be closer to the Blacks than to any of the Israeli Jewish groups. We have shown that Jews share common features, a fact that points to a common ancestry. A certain degree of admixture with their pre-immigration neighbors exists despite the cultural and religious constraints against intermarriage.

Wilson disease (WND) is an autosomal recessive disorder that is due to an inability of the liver to eliminate copper. Copper buildup in the liver, brain, kidney, and other tissues can result in liver cirrhosis, neurologic and psychiatric defects, and other problems. We have localized the disease-containing region to between D13S31 and D13S59, with > 70 multiply affected families, and have constructed a YAC contig of > 4.5 Mb that spans these loci and orders nine highly polymorphic microsatellites. Here we present an analysis of disequilibrium with markers in this interval and provide evidence for strong allelic associations between AFM084xc5 alleles and WND alleles in European, Middle Eastern, and East Asian populations. Significant but weaker allelic associations were also observed between WND alleles and alleles at D13S137 and D13S169. The strength of the association between AFM084xc5 and WND in all non-Sardinian populations combined (linkage-disequilibrium coefficient [phi] = .61) suggests that the number of mutations accounting for WND is less than expected on the basis of the variety of clinical symptoms that are observed.

Wilson disease (WD), an autosomal recessive disorder of copper metabolism, has been previously mapped to chromosome 13q. Highly informative PCR-based polymorphic microsatellites closely linked to the WD locus (WND) at 13q14.3, as well as sequence-tagged sites for closely linked loci, are described. Two polymorphic microsatellite markers at D13S118 and D13S119 lie within 3 cM of WND. Two others (D13S227 and D13S228) were derived from a yeast artificial chromosome containing D13S31. These were placed on a genetic linkage map of chromosome 13 and were typed in 74 multiplex WD families from a variety of geographic origins (166 affected members). Multipoint analysis provides very high odds that the location of WND is between D13S31/D13S227/D13S228 and D13S59. Previous odds with RFLP-based markers were only 7:1 more likely than any other location. Current odds are 5,000:1. Preclinical testing of three cases of WD by using the highly informative polymorphic microsatellite markers is described. The markers described here ensure that 95% of predictive tests using DNA from both parents and from at least one affected sib will have an accuracy > 99%.

Linkage of both several chromosome 13 DNA markers and the locus for the red cell enzyme esterase D (ESD) to Wilson disease (WD), an autosomal recessive disorder affecting copper metabolism, was investigated in five Middle-Eastern kindreds. The single-copy probe 7D2, identifying the polymorphic region D13S10, was demonstrated to lie 7.5 centiMorgans (cM) from the locus, since a maximum lod score of 4.66 at a recombination frequency of .07 (7.5 cM) was found between the locus for WD (WND) and D13S10. Multipoint linkage analysis between several chromosome 13 markers and WND enables us to propose that the order of markers closely linked to WND is as follows: centromere-D13S10-ESD-WND.