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Short tandem repeat polymorphisms on the male-specific part of the human Y-chromosome (Y-STRs) are valuable tools in many areas of human genetics. Although their paternal inheritance and moderate mutation rate (~10-3 mutations per marker per meiosis) allow detecting paternal relationships, they typically fail to separate male relatives. Previously, we identified 13 Y-STR markers with untypically high mutation rates (>10-2 ), termed rapidly mutating (RM) Y-STRs, and showed that they improved male relative differentiation over standard Y-STRs. By applying a newly developed in silico search approach to the Y-chromosome reference sequence, we identified 27 novel RM Y-STR candidates. Genotyping them in 1,616 DNA-confirmed father-son pairs for mutation rate estimation empirically highlighted 12 novel RM Y-STRs. Their capacity to differentiate males related by 1, 2, and 3 meioses was 27%, 47%, and 61%, respectively, while for all 25 currently known RM Y-STRs, it was 44%, 69%, and 83%. Of the 647 Y-STR mutations observed in total, almost all were single repeat changes, repeat gains, and losses were well balanced; allele length and fathers' age were positively correlated with mutation rate. We expect these new RM Y-STRs, together with the previously known ones, to significantly improving male relative differentiation in future human genetic applications.

Nonrecombining Y-chromosomal microsatellites (Y-STRs) are widely used to infer population histories, discover genealogical relationships, and identify males for criminal justice purposes. Although a key requirement for their application is reliable mutability knowledge, empirical data are only available for a small number of Y-STRs thus far. To rectify this, we analyzed a large number of 186 Y-STR markers in nearly 2000 DNA-confirmed father-son pairs, covering an overall number of 352,999 meiotic transfers. Following confirmation by DNA sequence analysis, the retrieved mutation data were modeled via a Bayesian approach, resulting in mutation rates from 3.78 x 10(-4) (95% credible interval [CI], 1.38 x 10(-5) - 2.02 x 10(-3)) to 7.44 x 10(-2) (95% Cl, 6.51 x 10(-2) - 9.09 x 10(-2)) per marker per generation. With the 924 mutations at 120 Y-STR markers, a nonsignificant excess of repeat losses versus gains (1.16:1), as well as a strong and significant excess of single-repeat versus multirepeat changes (25.23:1), was observed. Although the total repeat number influenced Y-STR locus mutability most strongly, repeat complexity, the length in base pairs of the repeated motif, and the father's age also contributed to Y-STR mutability. To exemplify how to practically utilize this knowledge, we analyzed the 13 most mutable Y-STRs in an independent sample set and empirically proved their suitability for distinguishing close and distantly related males. This finding is expected to revolutionize Y-chromosomal applications in forensic biology, from previous male lineage differentiation toward future male individual identification.

Isoelectric focusing has revealed that human complement factor I (CFI) is controlled by two polymorphic alleles, CFI(*)A and CFI(*)B, and a few rare variant alleles. In this study the molecular basis of the CFI polymorphism was investigated in 174 Japanese. The CFI(*)A was divided into two suballeles, CFI(*)As (R201S) and CFI(*)Ah (R406H). CFI(*)Aj, a rare variant allele originating from CFI(*)Ah, had an additional mutation (R502L). The distribution of these three mutations and two registered SNPs was investigated in a total of 2,471 individuals in 20 populations from various areas, and six haplotypes were observed. Haplotype H3, which is characterized by CFI(*)As, was found only in Far East populations: the frequencies were about 0.03 in the main island of Japan and lower than 0.01 in Okinawa and Korea. Haplotype H5, characterized by CFI(*)Ah, prevailed almost exclusively in East Asians and was observed at the highest frequencies in southern Chinese Han and Thais. CFI(*)Ah must have arisen in a southeastern part of Asia and thereafter have spread to neighboring populations.

The Y-STR DYS19 is firmly established in the repertoire of Y-chromosomal markers used in forensic analysis yet is poorly understood at the molecular level, lying in a complex genomic environment and exhibiting null alleles, as well as duplications and occasional triplications in population samples. Here, we analyse three null alleles and 51 duplications and show that DYS19 can also be involved in inversion events, so that even its location within the short arm of the Y chromosome is uncertain. Deletion mapping in the three chromosomes carrying null alleles shows that their deletions are less than approximately 300 kb in size. Haplotypic analysis with binary markers shows that they belong to three different haplogroups and so represent independent events. In contrast, a collection of 51 DYS19 duplication chromosomes belong to only four haplogroups: two are singletons and may represent somatic mutation in lymphoblastoid cell lines, but two, in haplogroups G and C3c, represent founder lineages that have spread widely in Central Europe/West Asia and East Asia, respectively. Consideration of candidate mechanisms underlying both deletions and duplications provides no evidence for the involvement of non-allelic homologous recombination, and they are likely to represent sporadic events with low mutation rates. Understanding the basis and population distribution of these DYS19 alleles will aid in the utilisation and interpretation of profiles that contain them.

Very little is known about the genes and mechanisms affecting skin lightening in Asian populations. In this study, two coding SNPs, c.G1129A (R163Q) at the MC1R (melanocortin 1 receptor) gene and c.A1962G (H615R) at the OCA2 (oculocutaneous albinism type II) gene, were investigated in a total of 1,809 individuals in 16 populations from various areas. The Q163 and R615 alleles prevailed almost exclusively in East and Southeast Asian populations. Wright's F (ST) was 0.445 for R163Q and 0.385 for H615R among the 16 populations. The frequency of the Q163 allele was higher in Northeast Asians than in Southeast Asians. The frequency of the R615 allele was highest in South China and unlikely to be associated with levels of ultraviolet radiation. This allele may be a good marker to study the genetic affinity among East Asians because of its restricted distribution and marked difference in allele frequency.

Haplotype frequencies for 11 Y-STR markers (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385, DYS437, DYS438 and DYS439) in a Romani population (n=63) from Slovakia, Jats of Haryana (n=84) and Jat Sikhs (n=80) from India were determined. The Slovakian Romani, the Haryana and Sikh populations were endogamous based on their unique haplotype ratio and haplotype diversity values, although the Sikh population appeared to be more diverse. AMOVA revealed non-significant differences between the Romanies and significant differences with non-Romani populations. The Macedonian Romani population differed from all Romani populations examined. Frequent haplotypes observed in Romani populations were sporadic in northwest Indian populations. Thirteen out of 316 populations worldwide were found to share the six most frequent haplotypes of the Slovakian Romanies when the screening conditions were narrowed based on the population size to be over 40, the occurrence of the haplotypes was more than one and the sum frequencies of the most frequent haplotypes was at least 0.02. The most common haplotypes were also observed in other Romani groups. When searching with two Indian (Malbar and Malaysian Indian) most frequent haplotypes under the same conditions matches could be detected in all Romani populations except for the Macedonian Romanies. The search with the Jat Sikhs and Jats of Haryana most frequent haplotypes resulted no matches in Romani populations.

Manipulation of urine sampling in sports drug testing is considered a violation of anti-doping rules and is consequently sanctioned by regulatory authorities. In 2003, three identical urine specimens were provided by three different athletes, and the identity of all urine samples was detected and substantiated using numerous analytical strategies including gas chromatography-mass spectrometry with steroid and metabolite profiling, gas chromatography-nitrogen/phosphorus detector analysis, high-performance liquid chromatography-UV fingerprinting, and DNA-STR (short tandem repeat) analysis. None of the respective athletes was the donor of the urine provided for doping analysis, which proved to be a urine sample collected from other unidentified individual(s). Samples were considered suspicious based on identical steroid profiles, one of the most important parameters for specimen individualization in sports drug testing. A database containing 14,224 urinary steroid profiles of athletes was screened for specific values of 4 characteristic parameters (ratios of testosterone/epitestosterone, androsterone/etiocholanolone, androsterone/testosterone, and 5alpha-androstane-3alpha,17beta-diol/5beta-androstane-3alpha,17beta-diol) and only the three suspicious samples matched all criteria. Further metabolite profiling regarding indicated medications and high-performance liquid chromatography-UV fingerprinting substantiated the assumption of manipulation. DNA-STR analyses unequivocally confirmed that the 3 urine samples were from the same individual and not from the athletes who provided DNA from either buccal cell material or blood specimens. This supportive evidence led to punishment of all three athletes according to the rules of the World Anti-Doping Agency. Application of a new multidisciplinary strategy employing common and new doping control assays enables the detection of urine substitution in sports drug testing.

Human orosomucoid (ORM), or alpha(1)-acid glycoprotein, is known to be controlled by duplicated and triplicated genes on chromosome 9, encoding ORM1 and ORM2 proteins. In this study, the structure and diversity of the ORM gene were investigated in 16 Sub-Saharan Africans, who originated from widely dispersed locations in Africa. The duplicated ORM1-ORM2 gene was observed in all 16 samples. ORM1*S1(2), characterized by an ORM2 gene-specific sequence in intron 5, was common in Africans. Three Africans showed the duplication of the ORM1 gene. The organization of the triplicated ORM1A-ORM1B-ORM2 gene was established in two Africans. The recombination breakpoints resulting in the ORM1 duplication lay within a small genomic interval around exon 1 of the ORM1B gene. The duplication of the ORM2 gene reported previously was not detected in this population sample. Several single-nucleotide polymorphisms were observed in the ORM2 gene. The rearrangement of the ORM gene is likely to occur often in Africans.

To test for human population substructure and to investigate human population history we have analysed Y-chromosome diversity using seven microsatellites (Y-STRs) and ten binary markers (Y-SNPs) in samples from eight regionally distributed populations from Poland (n = 913) and 11 from Germany (n = 1,215). Based on data from both Y-chromosome marker systems, which we found to be highly correlated (r = 0.96), and using spatial analysis of the molecular variance (SAMOVA), we revealed statistically significant support for two groups of populations: (1) all Polish populations and (2) all German populations. By means of analysis of the molecular variance (AMOVA) we observed a large and statistically significant proportion of 14% (for Y-SNPs) and 15% (for Y-STRs) of the respective total genetic variation being explained between both countries. The same population differentiation was detected using Monmonier's algorithm, with a resulting genetic border between Poland and Germany that closely resembles the course of the political border between both countries. The observed genetic differentiation was mainly, but not exclusively, due to the frequency distribution of two Y-SNP haplogroups and their associated Y-STR haplotypes: R1a1*, most frequent in Poland, and R1*(xR1a1), most frequent in Germany. We suggest here that the pronounced population differentiation between the two geographically neighbouring countries, Poland and Germany, is the consequence of very recent events in human population history, namely the forced human resettlement of many millions of Germans and Poles during and, especially, shortly after World War II. In addition, our findings have consequences for the forensic application of Y-chromosome markers, strongly supporting the implementation of population substructure into forensic Y chromosome databases, and also for genetic association studies.

In this study, the structure of the α1-acid glycoprotein (AGP), or orosomucoid (ORM), gene was investigated in a Ghanaian mother and her child, who shared an unusual variant, ORM1 S2(C), found by isoelectric focusing. Three remarkable changes of nucleotide sequence were observed: (1) The two ORM1 alleles, ORM1 * S and ORM1 * S2(C), had the AGP2 gene-specific sequence at one and three regions, respectively, in exon 5 to intron 5. The variant allele originating from ORM1 * S was characterized by a G-to-A transition, resulting in an amino acid change from valine to methionine, which is also detected in ORM1 F2, a form that is common in Europeans. (2) The AGP2 gene of the child, inherited from the father, was duplicated, as revealed by long-range polymerase chain reaction. (3) Three new mutations were observed in two exons of the AGP2 genes of the mother and child. All of these novel genomic rearrangements, which were not observed in Japanese subjects, may have arisen through point mutation, gene conversion, and unequal crossover events. It is likely that the rearrangement of the AGP gene has often occurred in Africans.

We have utilized computational biology to screen GenBank for the presence of recently integrated Ya5 and Yb8 Alu family members. Our analysis identified 2640 Ya5 Alu family members and 1852 Yb8 Alu family members from the draft sequence of the human genome. We selected a set of 475 of these elements for detailed analyses. Analysis of the DNA sequences from the individual Alu elements revealed a low level of random mutations within both subfamilies consistent with the recent origin of these elements within the human genome. Polymerase chain reaction assays were used to determine the phylogenetic distribution and human genomic variation associated with each Alu repeat. Over 99 % of the Ya5 and Yb8 Alu family members were restricted to the human genome and absent from orthologous positions within the genomes of several non-human primates, confirming the recent origin of these Alu subfamilies in the human genome. Approximately 1 % of the analyzed Ya5 and Yb8 Alu family members had integrated into previously undefined repeated regions of the human genome. Analysis of mosaic Yb8 elements suggests gene conversion played an important role in generating sequence diversity among these elements. Of the 475 evaluated elements, a total of 106 of the Ya5 and Yb8 Alu family members were polymorphic for insertion presence/absence within the genomes of a diverse array of human populations. The newly identified Alu insertion polymorphisms will be useful tools for the study of human genomic diversity.

The reference database of highly informative Y-chromosomal short tandem repeat (STR) haplotypes (YHRD), available online at http://ystr.charite.de, represents the largest collection of male-specific genetic profiles currently available for European populations. By September 2000, YHRD contained 4688 9-locus (so-called "minimal") haplotypes, 40% of which have been extended further to include two additional loci. Establishment of YHRD has been facilitated by the joint efforts of 31 forensic and anthropological institutions. All contributing laboratories have agreed to standardize their Y-STR haplotyping protocols and to participate in a quality assurance exercise prior to the inclusion of any data. In view of its collaborative character, and in order to put YHRD to its intended use, viz. the support of forensic caseworkers in their routine decision-making process, the database has been made publicly available via the Internet in February 2000. Online searches for complete or partial Y-STR haplotypes from evidentiary or non-probative material can be performed on a non-commercial basis, and yield observed haplotype counts as well as extrapolated population frequency estimates. In addition, the YHRD website provides information about the quality control test, genotyping protocols, haplotype formats and informativity, population genetic analysis, literature references, and a list of contact addresses of the contributing laboratories.

Alpha2-HS glycoprotein (AHSG), which is equivalent to fetuin in other species, is a protein found in human plasma. AHSG is polymorphic with two common alleles and many variants. To examine the intragenic haplotypes and their diversity at this locus, a contiguous genomic DNA sequence (10.3 kb) was analyzed in 20 samples (40 chromosomes), and haplotypes were determined for 309 subjects. Judging from the aligned nucleotide sequences and the conserved amino acid residues comparing human and chimpanzee AHSG, it was concluded that the type 1 allele is probably older and has evolved into four major suballeles. The type 2 allele was generated from one branch of the type 1 allele. AHSG*3 and *5 variants were each found to have a single nucleotide change in exon 7, resulting in the change of an amino acid residue from Arg299 to Cys and from Asp258 to Asn, respectively. It was noted that the AHSG*3 mutation gives rise to an additional cysteine residue, which possibly affects the conformation of the protein. The AHSG gene was found to have a low mutation rate and no apparent recombination events. Furthermore, the detected substitutions were nonhomogeneously distributed at this locus. In particular, four nonsynonymous substitutions were concentrated in the carboxyl-terminal domain.

A number of applications of analysis of human Y-chromosome microsatellite loci to human evolution and forensic science require reliable estimates of the mutation rate and knowledge of the mutational mechanism. We therefore screened a total of 4,999 meioses from father/son pairs with confirmed paternity (probability >/=99. 9%) at 15 Y-chromosomal microsatellite loci and identified 14 mutations. The locus-specific mutation-rate estimates were 0-8. 58x10-3, and the average mutation rate estimates were 3.17x10-3 (95% confidence interval [CI] 1.89-4.94x10-3) across 8 tetranucleotide microsatellites and 2.80x10-3 (95% CI 1.72-4.27x10-3) across all 15 Y-chromosomal microsatellites studied. Our data show a mutational bias toward length increase, on the basis of observation of more repeat gains than losses (10:4). The data are in almost complete agreement with the stepwise-mutation model, with 13 single-repeat changes and 1 double-repeat change. Sequence analysis revealed that all mutations occurred in uninterrupted homogenous arrays of >/=11 repeats. We conclude that mutation rates and characteristics of human Y-chromosomal microsatellites are consistent with those of autosomal microsatellites. This indicates that the general mutational mechanism of microsatellites is independent of recombination.

At least 815 meioses were studied in the HinfI polymorphisms of DNA minisatellite loci D1S7, D2S44, D7S21, D7S22, and D12S11 in order to collect data on respective mutation rates. At locus D7S21 (probe MS31) a striking difference between the paternal and maternal mutation rate was observed (1.5% versus 0.2%). This study also describes, how to deal biostatistically with paternal mutations in parentage testing. Possible implications of mutations are illustrated by the description of 2 cases. Case 1 reports an "exclusion" of mother and father with probe MS1. Case 2 describes 2 paternal "exclusions" with probes MS31 and G3. The statistical likelihood for a paternal "exclusion" with 2 of the 5 probes is 0.13%. By omitting probe MS1, this frequency can be reduced to 0.02%. Nevertheless, the second case clearly shows, that informative blood group markers cannot be replaced by DNA polymorphisms.

In this study, a short tandem repeat (STR) polymorphism in intron 7 of the human complement factor I (CFI) gene was studied in 637 DNA samples obtained from African, German, Thai, and Japanese populations and German and Japanese families. A total of 41 alleles were observed and classified into two groups, L and H, based on size differences. Group H, which consisted of 16 alleles, was observed only in Thai and Japanese populations at frequencies of 0.162 and 0.116, respectively, and was strongly associated with c.1217A in exon 11 (CFI*Ah). The heterozygosity values ranged from 0.89 in German to 0.93 in Thai populations. This STR would be a useful supplementary marker for forensic individualization.

A parentage case is described that revealed a potentially erroneous exclusion from paternity in three systems, two on chromosome 21 and one on chromosome Y. Follow-up tests, especially of chromosome 21, were subsequently performed. Actually, the child's chromosome 21 showed alleles of maternal but not of paternal origin being consistent with a maternal uniparental disomy of chromosome 21. The third genetic incompatibility was observed at the Y chromosome and attributed to a usual one-step de novo mutation. This case is emphasizing the (generally adopted) requirement that an exclusion from paternity must not be based on the absence of paternal alleles at genetic systems all located on the same chromosome. In fact, the need for extended typing programmes is demonstrated.

The Y-chromosomal short tandem repeat (Y-STR) polymorphisms included in the AmpFlSTR® Yfiler® polymerase chain reaction amplification kit have become widely used for forensic and evolutionary applications where a reliable knowledge on mutation properties is necessary for correct data interpretation. Therefore, we investigated the 17 Yfiler Y-STRs in 1,730–1,764 DNA-confirmed father–son pairs per locus and found 84 sequence-confirmed mutations among the 29,792 meiotic transfers covered. Of the 84 mutations, 83 (98.8%) were single-repeat changes and one (1.2%) was a double-repeat change (ratio, 1:0.01), as well as 43 (51.2%) were repeat gains and 41 (48.8%) repeat losses (ratio, 1:0.95). Medians from Bayesian estimation of locus-specific mutation rates ranged from 0.0003 for DYS448 to 0.0074 for DYS458, with a median rate across all 17 Y-STRs of 0.0025. The mean age (at the time of son’s birth) of fathers with mutations was with 34.40 (±11.63) years higher than that of fathers without ones at 30.32 (±10.22) years, a difference that is highly statistically significant (p 1%, 12 had mutation rates of >0.1% and four of

BamHI polymorphism at the VNTR locus D2S44 was investigated, concentrating on band frequencies, mutation rate and confirmation of Mendelian inheritance. In this series 39 restriction fragments showing frequencies less than 10% could clearly be distinguished. No mutations could be observed and the Mendelian character of inheritance is beyond reasonable doubt.

Asians as well as Europeans have light skin, for which no genes to date are known to be responsible. A mutation, Ala481Thr (c.G1559A), in the oculocutaneous albinism type II (OCA2) gene has approximately 70% function of the wild type allele in melanogenesis. In this study, the distribution of the mutation was investigated in a total of 2,615 individuals in 20 populations from various areas. OCA2*481Thr prevailed almost exclusively in a northeastern part of Asia. The allele frequency was highest in Buryat (0.24) in Mongolia and showed a north–south downward geographical gradient. These findings suggest that OCA2*481Thr arose in a region of low ultraviolet radiation and thereafter spread to neighboring populations.

The membrane-associated transporter protein (MATP) plays an important role in melanin synthesis. The L374F mutation in the SLC45A2 gene encoding MATP has been suggested to be associated with skin colour in major human populations. In this study more detailed distribution of the F374 allele was investigated in 1649 unrelated subjects from 13 Eurasian populations and one African population. The highest allele frequency was observed in Germans (0.965); French and Italians showed somewhat lower frequencies; and Turks had an intermediate value (0.615). Indians and Bangladeshis from South Asia were characterized by low frequencies (0.147 and 0.059, respectively). We also found the F374 allele in some East and Southeast Asian populations, and explained this by admixture. Haplotype analysis revealed that the haplotype diversity was much lower in Germans than in Japanese, and suggest that the L374F mutation occurred only once in the ancestry of Caucasians. The large differences in distribution of the F374 allele and its haplotypes suggest that this allele may be an important factor in hypopigmentation in Caucasian populations.

This paper presents 5 examples of complicated deficient parentage cases, which were sufficiently resolved by extensive DNA typing using short tandem repeat (STR) and restriction fragment length polymorphisms (RFLPs). The latter have greatly contributed to the solution of deficiency cases, although their application is only feasible, if high molecular weight DNA and time are in abundance. This apart, RFLP technique is available in a few laboratories only, and its extinction can be expected in medium term. This development will pose a problem unless more highly polymorphic STR systems are at the service of forensic genetic laboratories. The required "new" additional STR polymorphisms must be able to fully replace RFLPs in terms of their respective information content. STR loci of this quality are e.g. ACTBP2 (SE33), D5S2360, and gonosomal loci. Moreover, the newly introduced STR kit "Humantype Chimera" is considered valuable from this point of view.

Novel polymorphic sites within the coding region of the human coagulation factor XIII A-subunit (F13A) gene and their haplotypic combinations with the other polymorphic sites thus far reported are presented. Polymorphic bands were detected in exons 2, 5, 8, 12 and 14 by using single strand conformational polymorphism analysis and antithetic forms of the polymorphic exons were linked with each other, cosegregating as distinct sequence haplotypes. In Finnish, German, and Russian populations a total of 18 haplotypes were observed of possible 72 haplotypic combinations of the 5 exons. Ten of the haplotypes detected were found to have no novel mutations but to be only combinations of preexisting mutations. No tightly associated combinations in pairwise comparisons between antithetic forms of the polymorphic exons were observed, indicating that there may be recombinational hotspots within the F13A gene region.

The two polymorphic alleles of esterase D (ESD), ESD*5 and ESD*7, are specific to Europeans and Asians, respectively. In this study the molecular basis was characterized: ESD*5, arising from ESD*1, has a G to A transition, resulting in Gly257 (GGT)→Asp(GAT); and ESD*7, originating from ESD*2, has an A to G transition, resulting in Asp 231 (GAT)→ Gly(GGT). Glycine is also involved in the common ESD*1/ESD*2 polymorphism [Gly190 (GGA)→Glu(GAA)]. Haplotype analysis using a few novel intragenic polymorphisms showed strong associations among polymorphic sites, suggesting that recombination has been less frequent in the human ESD gene, although it spans about 25 kb from exon 1 to exon 10. A marked difference was observed in the distribution of haplotype frequencies between Germans and Japanese.

In a German paternity test, an alleged father was excluded only by reverse homozygosity of ORM1 phenotypes (mother ORM1 S, child ORM1 S and alleged father ORM1 F1) out of the 28 classical and DNA markers investigated. Without the ORM1 system the biostatistical probability of paternity was calculated to exceed 99.9999%. The intensity of the immunoprinted bands of the ORM1 protein for the child and alleged father after isoelectric focusing appeared to be reduced to about half. To identify a possible null allele, gene-specific amplification followed by single-strand conformation polymorphism and sequencing analyses were carried out. Deletion of one of the two copies of a 4 bp direct repeat sequence (GTCT) in exon 4 of the consensus sequence of ORM1*F1 was observed in the child and alleged father. Thus, the sharing of a rare mutant gene, ORM1*Q0koln, increased the probability of paternity.

We have studied the sequence structure and population genetics of a ‘new' short tandem repeat polymorphism at locus D5S2360 in German Caucasians. Sequencing at this locus revealed a considerable variation, which is characterized by a tetranucleotide (AGAT) n repeat pattern with (GAT), (AGATT), and (AG) repeats dispersed throughout the alleles. These microvariations do not necessarily alter the size of the alleles. They may vary by one or two pairs or they may remain unchanged in size. At locus D5S2360 we observed 33 allelic lengths comprising at least 36 different alleles. Population data revealed a high polymorphism with a heterozygosity rate of approximately 92.5%.

This study provides Jat Sikhs population data in North India for nine short tandem repeat (STR) loci.

A total of 215 paternity cases were analysed after testing 24 marker systems. Despite technical advantages of polymerase chain reaction related polymorphisms (automatisation, employment of robots, lesser requirements concerning of quality and quantity of DNA) it could be shown that the exclusive employment of a parentage testing kit is compromised by an increased risk of erroneous conclusions. It is estimated that in about 3–4% of the cases ambiguous situations have to be expected which are caused by the occurrence of single or double exclusions. In these cases it is impossible to decide whether the exclusions indicate either true nonpaternity or a de novo mutation. The situation might become even more complicated if an involvement of a close relative of the alleged father cannot be ruled out. We cautiously advance the hypothesis that in parentage testing DNA minisatellite polymorphisms form an optimal set of tools.

The distribution of restriction fragments at the DNA minisatellite locus D16S309 was estimated by investigating blood samples from 2617 unrelated West German Caucasians and 1269 offspring. Furthermore segregation of fragments was studied in a large family and in trios. Altogether 2296 meioses were studied, revealing 7 paternal and 3 maternal mutations. Inspection of "phenotypes" did not reveal any remarkable deviation from Hardy-Weinberg equilibrium.

We report maternal and paternal mutation rates at loci DIS7 (MS1), D7S21 (MS31), D12S11 (MS43A), and D7S22 (G3). The respective mutation rates were as follows: System Maternal meioses Paternal meioses D1S7 4.3% 4.2% D7S21 0.2% 1.2% D12S11 0.05% 0.4% D7S22 0.1% 0.8% At loci D7S21, D12S11, and D7S22 statistically significant differences in mutation rates exist between the sexes. No such difference was observed at locus DIS7. However inspection of the latter data reveals that by mutation at spermiogenesis approximately two-thirds of the fragments showed an addition of repetitive units, while a 50: 50 ratio was encountered in the series of maternal mutations. We also report the observation of naturally occurring 3-fragment patterns.

Restriction fragment-length polymorphism of locus D2S44 detected by the highly polymorphic probe YNH24 and restriction endonuclease HaeIII can be used to improve parentage testing when representative fragment-size frequencies can be obtained. By joining the results of different laboratories, it is possible to set up a meaningful databank. Therefore, the same randomly chosen samples were tested for the HaeIII RFLP detected by probe YNH24 in Dusseldorf (DUS) and Amsterdam (AMS). The results of the different fragment-size calculations obtained by using internal markers and a computerized system (DUS-cad and AMS-cad), and by using external markers and manual calculations (DUS-man), were analyzed. Comparing these results, no statistically significant differences were seen. The results obtained with probe YNH24 and enzyme HaeIII in Dusseldorf and Amsterdam can be used to attain a sufficient number of samples to generate relevant fragment-size frequencies.

Using isoelectric focusing in thin-layer agarose gel (AGIF) with the narrow pH range of 4.5-5.4, a high resolution of esterase D (ESD) isozyme banding patterns has been achieved. Some variant phenotypes which could not be distinguished from common ESD types by conventional electrophoresis have shown different patterns after AGIF. The IEF method permitted the distinction of two further variants in the ESD system, tentatively named ESD Rehren and ESD Ravensburg. We recommend, therefore, that for the classification of ESD phenotypes a high resolution IEF technique should be used.

One hundred and fifty-five cord cells were tested for the red blood cell antigens Lua, Lub and Cob in order to collect data on the early postnatal expression of these markers. Additionally, dosage studies were carried out in 8–10-month-old heterozygous children. Antigens Lua and Lub revealed to be significantly less expressed in children of both ages compared with those of their mothers, whereas no such differences could be demonstrated in the expression of the antigen Cob.

By means of extensive serogenetic testing of a family, RFLP analysis and biostatistic evaluation we present evidence for the rate transmittance of a ‘silent’ information at the MN blood group locus in a Caucasian family.

Two groups of Chinese individuals of the city of Wuhan in the People's Republic of China, consisting of 98 blood bank donors and 278 workers in a steel factory, respectively, have been typed for G1m, G2m, G3m, A2m and Km allotypes. The Gm-A2m haplotype frequencies as well as the Km gene frequencies appeared to be quite similar in these two groups of people, the main haplotypes being Gmaf;n;b A2m2 and Gmza;..;g A2m1. After joining the data of the two groups, the frequencies of the main Gm haplotypes and the A2m and Km gene frequencies have been compared with those of six other Asian populations. In Asia, going from the south to the north, an increasing frequency of Gmza;..;g and a decreasing frequency of Gmaf;n;b were observed. The frequencies found in the investigated Chinese population lie between the frequencies found in the Chinese from Taiwan and the Japanese.

The Ta (transcribed, subset a) subfamily of L1 LINEs (long interspersed elements) is characterized by a 3-bp ACA sequence in the 3' untranslated region and contains approximately 520 members in the human genome. Here, we have extracted 468 Ta L1Hs (L1 human specific) elements from the draft human genomic sequence and screened individual elements using polymerase-chain-reaction (PCR) assays to determine their phylogenetic origin and levels of human genomic diversity. One hundred twenty-four of the elements amenable to complete sequence analysis were full length ( approximately 6 kb) and have apparently escaped any 5' truncation. Forty-four of these full-length elements have two intact open reading frames and may be capable of retrotransposition. Sequence analysis of the Ta L1 elements showed a low level of nucleotide divergence with an estimated age of 1.99 million years, suggesting that expansion of the L1 Ta subfamily occurred after the divergence of humans and African apes. A total of 262 Ta L1 elements were screened with PCR-based assays to determine their phylogenetic origin and the level of human genomic variation associated with each element. All of the Ta L1 elements analyzed by PCR were absent from the orthologous positions in nonhuman primate genomes, except for a single element (L1HS72) that was also present in the common (Pan troglodytes) and pygmy (P. paniscus) chimpanzee genomes. Sequence analysis revealed that this single exception is the product of a gene conversion event involving an older preexisting L1 element. One hundred fifteen (45%) of the Ta L1 elements were polymorphic with respect to insertion presence or absence and will serve as identical-by-descent markers for the study of human evolution.

A group of 300 unrelated and healthy individuals of Northrhine-Westphalia were screened for the red cell antigen Cob. The phenotype frequency of Co(b+) was found to be 7.3%.

This paper describes the very rare occurrence of subacute sclerosing panencephalitis (SSPE) in two siblings: a Turkish boy and his younger sister. The clinical picture was characteristic, and the diagnosis was confirmed in both cases by appropriate laboratory examination. The interval between the occurrence of the first neurological symptoms in the boy, and subsequently in the girl was four years. Study of HLA- and 27 other polymorphic marker-systems did not reveal linkage to one of the systems tested. Therapeutic trials in the girl included intravenous and intraventricular application of a total of 87 X 10(6) U human fibroblast interferon (Hu INF-beta) over 21 days. However, up to 3 months after the end of interferon administration there were no significant changes in the girl's condition.

Upon testing blood samples for medico-legal purpose, an exceptionally weak expression of the Rhesus antigen e was observed. There is evidence for the phenotype Rh2 $$\dot r$$ h which is rather unusual in white people. Apart from this, the low incidence antigen Cx has been found in two cases. Its mode of reaction with anti-C and anti-c sera is described.

The immunoglobulin allotypes G1m(1,2,3) and G3m(10,21) were typed in 2855 unrelated West German adult individuals. 1455 individuals were typed for the factors Km(1,3). Phenotype and haplotype frequencies are reported. The usefulness of this routine typing programme in paternity tests is demonstrated in three case reports.

Blood samples from 507 unrelated persons in Northrhine-Westphalia and from 254 paternity cases were tested for the Lutheran blood group antigens Lua and Lub. The gene frequencies were found to be 0.03 (= Lua) and 0.969 (= Lub).

Blood samples from 300 unrelated persons in Northrhine-Westphalia (F.R.G.) have been tested for the Doa (Dombrock) blood group antigen. 199 blood samples (66.3%) were found to be Do(a+).

Using "new" techniques (malic acid thin layer agarose gel electrophoresis and/or isoelectric focusing), the polymorphism of the human red cell isozyme system esterase D (ESD) was shown to be extended. We report the gene frequencies observed among 312 unrelated Caucasian individuals living in the Düsseldorf area. The finding of a "new" allele at the ESD locus is also described.