Abstract: We were fascinated to read the report of Drs. Schaap and Bach (1980) suggesting that Hunter's syndrome may be a "Jewish disease". A survey of Hunter's syndrome patients throughout the United Kingdom conducted by ourselves, confirms that the incidence of 1 in 67,500 obtained by Drs. Schaap and Bach is indeed very high. As shown in Fig. 1, the patients were evenly distributed throughout the United Kingdom with no evidence of geographical clustering. The diagnosis was confirmed either enzymatically (Archer et al. 1981) or genetically (undisputed Xlinked pedigree) in 66 of the 88 patients ascertained: in the remaining 22 the diagnosis was regarded as probable based on clinical observations and the pattern of mucopolysacchariduria. The full results of this study have been presented (Young 1981). The results indicate that the overall incidence of Hunter's syndrome in the United Kingdom was approximately 1 in 132,000 male live births during the years of maximum ascertainment (1955-1974). We recognise two forms of the disorder, mild and severe. The incidence of the latter was 3.38 times that of the former. Although some 600 paediatricians and geneticists throughout the United Kingdom were approached, it is certainly possible that the incidence figures we have derived are underestimates. However we would be very surprised if the patients we have ascertained represent less than 50% of all known cases in the United Kingdom, since we recewed wide-spread cooperation from centres known to have special expertise and interest in the mucopolysaccharidoses. We observed no particular increased incidence amongst the British Jewish community, although the ethnic origins of some patients were unknown. Thus we conclude that the remarkably high incidence observed by Drs. Schaap and Bach is indeed worthy of note. Their intriguing suggestion that it may be due to a previous shift in the sex ratio in favour of increased heterozygous females as opposed to hemizygous males, with subsequent increase in affected males due to contemporary disregard of the Jewish purity laws, could be easily tested by studying the menstrual cycle in Hunter heterozygotes. If such an explanation is valid then these ladies should have relatively short follicular phases of the menstrual cycle with ovulation occurring on approximately the 12th day, i.e. the day when marital relations would be resumed by those who practice ritual separation. It is difficult to imagine a physiological basis for such a ]phenomenon. Other possible explanations for this high incidence in Israeli Jews might include admixture of autosomal recessive cases.

Abstract: This paper surveys the literature on familial nonchromaffin paragangliomas and presents the results of a study of a family with 295 living members.

Abstract: We reviewed partial trisomy of the long arm of chromosome 7 after a new case was brought to our attention. The clinical differences between the various types of trisomies 7q were evaluated by statistical analysis, and three groups were defined. These groups correspond to the segments q22 or q21 leads to q31, q31 leads to qter, and q32 leads to qter, and would seem to represent three different syndromes, of which one is more serious than the other two.

Abstract: The genealogy of 14H-2K b mutations arising spontaneously in the C57BL/6Kh colony is presented together with data from skin-graft monitoring and husbandry procedures. Eight of the 14 mutations have phenotypic and structural similarities, but the pedigree analysis and evaluation of the histocompatibility genetics of their sibs and ancestors strongly indicate that they represent recurring mutational events rather than the segregation of a single mutation throughout the colony.

Abstract: Preliminary mapping of 346 cleavage sites in the mitochondrial genome of 100 human beings gives evidence that the genes for transfer RNA are highly variable, a result that points to the need for testing the accuracy of mitochondrial protein synthesis. In addition, the map comparisons imply that Australia has as much mtDNA diversity as any other area tested in the Old World. Assuming a model of strictly maternal inheritance, it appears possible to follow individual female lineages back hundreds of generations thereby providing human genetics with an important new measure of population heterogeneity. This measure, when compared with those available from protein and morphologic considerations, will help highlight particular groups of people whose mitochondria may increase greatly our understanding of the historical processes leading to the evolution of our own species.

Abstract: Introduction History of Human Genetics Human Genome Sequence and Variation Chromosomes From Genes to Genomics to Proteomics Formal Genetics of Humans: Modes of Inheritance Linkage Analysis for Monogenic Traits Oligogenic Disease Formal Genetics of Humans: Multifactorial Inheritance and Common Diseases Lessons from the Genome-Wide Studies for Complex Multifactorial Disorders and Traits Epigenetics Human Gene Mutation: Mechanisms and Consequences Human Hemoglobin Human Genetics of Infectious Diseases Gene Action: Developmental Genetics Cancer Genetics The Role of the Epigenome in Human Cancers Population Genetic Principles and Human Populations Consanguinity, Genetic Drift, and Genetic Diseases in Populations with Reduced Numbers of Founders Human Evolution Comparative Genomics Genetics and Genomics of Human Population Structure Genetic Epidemiology Pharmacogenetics Behavioral Genetics The Genetics of Personality Mental Retardation and Intellectual Disability Genetic Factors in Alzheimer Disease and Dementia Genetics of Autism The Genetics of Alcoholism and Other Addictive Disorders Behavioral Aspects of Chromosomal Variants Genetics of Schizophrenia and Bipolar Affective Disorder Model Organisms for Human Disorders Mouse as a Model for Human Disease Caenorhabditis elegans, A Simple Worm: Bridging the Gap Between Traditional And Systems-Level Biology Drosophila as a Model for Human Disease Human Genetics and the Canine System Fish as a Model for Human Disease Genetic Counseling and Prenatal Diagnosis Gene Therapy Cloning in Research and Treatment of Human Genetic Disease Genetic Medicine and Global Health Genetic Databases Databases and Genome Browsers EnsemblGenome Browser Databases in Human and Medical Genetics Subject Index.

Abstract: Genetic polymorphism of human plasminogen in the Japanese population has been described using polyacrylamide gel isoelectric focusing electrophoresis followed by immunofixation techniques. New variants PLG1′-1′, PLG2′-1, and rare 1 were detected. Fibrinolytic activity per milligram plasminogen of each phenotype, except for PLG1′-1′ and PLG1-1′, was within the normal range. The PLG1′ component was associated with no or less plasminogen activity, but possessed plasminogen antigen. Gene frequencies calculated from 750 individuals were PLG1; 0.9560, PLG2; 0.0113, PLG1; 0.0233, and PLG2; 0.094; respectively. The distribution of phenotypes fitted the Hardy-Weinberg equilibrium. In order to detect the plasminogen phenotypes the immunofixation technique was more suitable than the zymogram technique.

Abstract: The relative genome sizes and the proportions of X- and Y-chromosomal DNA in Drosophila hydei, D. neohydei and D. eohydei were measured by microspectrophotometry. Some implications of the results with respect to genome evolution in these species are discussed.

Abstract: Unlike the human class I major histocompatibility antigens, which are present on virtually all nucleated cells, class II (Ia-like) antigens, typified by the products of the H L A D R locus, are limited in their expression to B lymphocytes, macrophages, and a few other cell types (Geier and Cresswel11977, van Rood et al. 1975, Ko et al. 1979, Greaves et al. 1979). Resting T lymphocytes are for the most part devoid of Ia-like antigens, although several studies have suggested the existence of a small subpopulation of peripheral blood T cells which express these antigens (Fu et al. 1978, Ko et al. 1979, Greaves et al. 1979). It is not known whether this subpopulation represents a class of in vivo stimulated T cells or a true resting population, though most of the cells do not have the appearance of blasts. These cells, moreover, have been reported to be a subset of T7 cells, bearing Fc receptors for IgG (Greaves et al. 1979), whose classification as T cells has recently been questioned on the basis of monoclonal antibody studies (Reinherz et al. 1980). In any case, the majority of unstimulated T cells lack Ia-like antigens. Upon stimulation with lectins, soluble antigens, or in mixed lymphocyte culture, however, a variable and often large percentage of T cells express Ia-like antigens which are similar serologically to those of resting B lymphocytes (Ko et al. 1979, Greaves et al. 1979). Lysis of Ia-like-antigen-positive T cells with heteroantiserum and complement prior to stimulation does not eliminate expression of these antigens in the stimulated population, so at least a portion of the stimulated cells must express the antigens de novo. Conversely, a subpopulation of stimulated T cells always remains Ia-like-antigen negative, though this subpopulation may be quite small in some cases (Ko et al. 1979, Greaves et al. 1979). The pattern of Ia-like antigen expression on human lymphoblastoid cell lines (LCL) is similar to that of resting lymphocytes ; B-LCL express the antigens and T-

Abstract: Gm systems provide unique markers for the study of human genetics, especially for the characterization of a population, the study of gene flow, and genetic drift by the presence of a unique haplotype or by marked differences in the frequencies of identical haplotypes. It has been shown that Gm haplotypes commonly present among Mongoloids are Gmag, Gmaxg, Gmab3st, and Gmafb1b3.

Abstract: Matsuoka et al. (1981) recently reviewed t r isomy 18q in this journal . On the basis of 20 pat ients f rom the l i terature and one of their own patients, they came to the conclusion that the main picture of t r isomy 18 is due to the tr isomic state of 18q21. Other publications on fur ther cases (Jaffray et al. 1980; Turleau et al. 1980), which did not suppor t this hypothesis , were obviously not taken into considerat ion by the authors . In a kin with six carriers for the t ranslocat ion t(9;18)(p23; q122) we found one case (Pat ient S.R.) with part ial t r i somy 18 (q122-~qter), which has not been publ ished so far (Fig. 1). One proposi tus with part ial t r isomy 18 (p ter~q122) comes from a family observed by Jaff ray et al. This family shows a reciprocal t rans locat ion t(9;18) which is identical to tha t in our family. Thus bo th pat ients have the two tr isomic al ternat ives for ch romosome 18 and the same ba lanced t ranslocat ion. The patients provide an oppor tun i ty to compare the phenotypes (Table 1). In this connect ion it must be remembered that , due to the reciprocal t rans locat ion in the patients , a small deficiency and an equally small part ial tr isomy, respectively, resulted which in addi t ion can affect the phenotype . Table 1. The major signs of the two patients with partial trisomy 18

Abstract: Ia antigens which consist of two polypeptide chains, ~ and/~, are associated with a third chain of 31K, as first described by Jones and co-workers (1978). Up until now, no polymorphism could be detected for this 31K polypeptide, hence it has been designated the invariant ([i) chain. Whereas ~ and ]? chains of Ia antigens are known to be encoded by the immune response (I) region of the major histocompatibility complex on chromosome 17 of the mouse, the chromosome controlling the I i chain has not yet been identified, due mainly to the lack of allelic forms. I i chains were originally thought to be present only in the cytoplasm and not on the cell surface because immunoprecipitates of surface-labeled material with Ia antibodies did not contain I i chains (Jones et al. 1978). However, in the case of a monoclonal antibody (mAb) raised in a rat against the mouse I i chain and designated In-l, we have recently observed that I i chains are present on the surface of Ia positive lymphocytes (Koch et al. 1982). The specificity of mAb In-1 for the I i chain has been demonstrated by two-dimensional SDS-PAGE and SDSIEF gel systems (Koch et al. 1982) and by the observation that in a cell-free translation system, In-1 precipitates exclusively I~ chains (Lipp et al., in preparation). In addition, immunochemical studies with this mAb have demonstrated that I i polypeptides are associated with ia c~ and/~ chains only in the cytoplasm but not on the cell surface. This observation would explain why [i has not been detected on the cell surface when Ia antibodies have been used for immunoprecipitation. In the present work, we have used mAb In-1 in combination with mouse-hamster hybrids which have lost chromosome 17 to determine whether chromosome 17 also encodes the I i chain. The mouse-hamster hybrids have been produced by fusion of the GD36A hamster B cell line with BALB/c spleen cells. Their establishment, karyotypes, and other characteristics have been described in detail by Szymura and

Abstract: A family with trisomy-21 mosaicism in two successive generations and a Down's syndrome child in the third generation is presented. Cytogenetic studies of eight individuals of this family showed a marker chromosome 15ph+ and a heteromorphic chromosome 18 in some members. The standard trisomy 21 in the proband was derived from a trisomy-21 oogonium by secondary nondisjunction in his mother.

Abstract: A 7-month-old male with trigonocephaly, hypotelorism, cleft palate, and agenesis of the corpus callosum was found to have an extra band within the qh+ region of one of his chromosomes 9; cytogenetic studies of his family revealed that the \"variant\" chromosome 9 had been inherited from his clinically normal father (Fig. 1). The relationship of the cytogenetic finding to the phenotype of the patient is unknown since the same variant chromosome has been found in normal individuals and in patients with different clinical features (Madan 1978; Sutherland 1981).

Abstract: A de novo interstitial deletion [46,XY,del(1)(pter--+q23::q25 --+qter)] was detected in a 1620-g infant born after 40 weeks gestation to an 18-year-old mother of Polish descent and a 23-year-old father of Hispanic descent. The father had worked in a chemical factory for 11/., years prior to conception of the proband. The proband's only sib, a female, is said to be normal. Gestation was characterized by intrauterine growth retardation and oligohydramnios. The infant showed facial dysmorphisms reminiscent of trisomy 13 (sloping forehead, broad nasal bridge, bilateral cleft lip and palate), but no eye anomalies were evident. Other anomalies included brachydactyly, bilateral clinodactyly V, left distal transverse palmar crease, and bilateral equinovarus. No other anomalies were revealed by roentgenographic or ultrasonographic studies, including those of the kidneys and head. Nonetheless, the infant developed renal failure and died 6 days after birth in cardiac arrest. Necropsy was not permitted. The interstitial deletion was present in all 58 (GTG-banded) metaphases derived from cord blood cultures (lymphocytes) and in all 18 metaphases derived from fibroblast cultures. Chromosomal complements of both parents were normal. Clinical features, prognosis, and associated risk factors characteristic of autosomal interstitial deletions need to be elucidated. We would therefore be interested in corresponding with others who have observed interstitial deletions involving chromosome no. I. A New Case of Satellited Yq Chromosome

Abstract: Cytogenetic analysis from lymphocytes and skin fibroblasts of a 2-day-old girl with some minor anomalies, revealed a partial trisomy lq and a partial monosomy Xq in all cells (Wegner et al. to be published). The unbalanced karyotype of the girl was due to malsegregation of the maternal translocation chromosomes t (X; 1) (q22;q21). With respect to the "critical region hypothesis" (Sarto et al. 1973; Summitt et al. 1978), the fertility of the mother being a translocation carrier is unexpected because gonadal dysgenesis should be the consequence of a break in the region Xq 13 to Xq26 including Xq22. To my knowledge up to now two exceptions to the "critical region hypothesis" have been described with the same breakpoint in Xq22 (Barnabei et al. 1981; Madan et al. 1981). ! would like to receive information about further exceptional cases to learn if the breakpoints are located constantly in Xq22 or are distributed more generally over the whole "critical region". References

Abstract: Chromosomal replication was studied by means of the BrdU-Hochst-Giemsa-technique in three murine T-cell leukemias with special regard to chromosome 15. In all the three leukemic cell lines the normally early replicating band 15 E was undetectable whereas late replication in this region is completely unaltered. Furthermore, R-banding, the structural homologue of early replication banding, remains unchanged. This observation is interpreted as a shift in the time point of replication during the S-phase of region 15 E, though the exact timing of replication of this region in tumor chromosomes remains unresolved.

Abstract: The X-linked α subunit of larval serum protein 1 (LSP1-α) is shown to lack dosage compensation in six members of the melanogaster species subgroup, viz., Drosophila melanogaster, D. simulans, D. mauritiana, D. erecta, D. yakuba, and D. teissieri, by quantitative filter hybridization and by electrophoretic and autoradiographic analyses of fat body proteins. These results support the hypothesis that there is little selection pressure on the LSP1-α gene to acquire dosage compensation.

Abstract: The gen e for human esterase-D has been assigned to chromosome 13 by means of somatic cell hybridization (Chen et al. 1975). Family studies on the linkage data of esterase-D to the centromere of chromosome 13 prompted Robson et al. (1976) and Gray et al. (1978) to suggest the assignment of esterase-D to the distal segment of 13q, namely to bands 13q32 or 13q33. However, this was challenged by the fact that the heterozygous electrophoretic pattern of ESD 2-1 was found in patients with deletion of 13q32--'13q34 (Turleau et al. 1978; Emanuel et al. 1979), and that no reduction ofesterase-D activity was found in a de novo case of 46,XX,del(13)(q32) compared to her karyotypically normal parents (Telfer et al. 1980). By measuring the gene-dosage effect in five patients with various aberrations of chromosome 13, Sparkes et al. (1980) were able to assign the gene for human esterase-D to band 13q14. This was subsequently confirmed by Mohandas et al. (1981) and Rivera et al. (1981) on four further patients using similar methods. We present here two patients with aberrations of chromosome 13 (Table I), whose activities of erythrocyte esterase-D (Sparkes et al. 1979) confirmed the above assignment. Patient 1 was monosomic for the segment 13q12--+13q21 and his esterase-D activity was only about half of his parents. Patient 2 was trisomic for the segment 13q21.2~13qter, and his esterase-D activity was not higher than his parents. Thus, our results do not contradict the assignment of esterase-D to band 13q14. Based on the data ofgene-dosage effect, either by inclusion or exclusion of approximately 50% increase of activity in duplication and approximately 50% decrease of activity in deficiency, the gene for human esterase-D seems to be located within the band 13q14 in the close vicinity of the gene for retinoblastoma. The prospective clinical application of this close linkage has been discussed by Sparkes et al. (1980).

Abstract: A study was carried out on C-banded chromosomes 1, 9, 16, Y from an unselected population and from 30 normal families. We found: a) great variability in length and position of the C-bands; b) somatic mosaicism involving C-bands; c) variants in children that were not present in parental patterns. The possible role of crossing-over in generating the last two phenomena is discussed.

Abstract: The major envelope protein of murine leukemia virus (MuLV), gp70, is known to be expressed on thymocytes of certain mouse strains which rarely, if ever, express complete virions (Tung et al. 1975a, b). The occurrence of this virally encoded protein was originally detected because in some strains it carries the antigen G~x (Tung et al. 1975a, Stockert et al. 1971). Classically G~x has been described as an antigen characteristic of the thymic stage of T-cell differentiation, analogous in this respect to TL antigens. In G~x + strains such as 129, G~x can be detected on the surface of thymocytes but not on spleen cells (Stockert et al. 1971). Some Glxmouse strains such as C57BL/6 (B6) express gp70 molecules lacking the G~x antigen on thymocytes (Tung et al. 1975b). A few strains exhibit no detectable gp70, G~x + or Glx -. An interesting example of this sort of mouse is the congenic 129-G~xstrain, in which the G~xphenotype of B6 has been crossed into the 129 strain (Stockert et al. 1975). This strain is also negative for the thymocyte-surface gp70 characteristic of B6 mice, thus demonstrating that the Gix + gp70 of 129 and the Gixgp70 of B6 are encoded at nonallelic genetic loci (Tung et al. 1975b). [In the 129 mouse the locus designated Gv-I probably contains the structural gene for Grx + gp70, since this locus is semidominant in genetic crosses (Stockert et al. 1971)]. As predicted by this model, the reciprocal congenic, B6-GIx ÷, expresses both species of gp70 on its thymocytes. By the use of broadly reactive hyperimmune anti-gp70 serum, we have found that spleen cells from 129, B6, and B6-GIx +, but not 129-G~x-, mice also express cell-surface gp70. The gp70 in spleen appears to be present on mature T cells and on at least one other cell type. The latter probably includes B cells, but conclusive evidence on this point is not yet available. In G~x + mice the occurrence of endogenously encoded gpT0 molecules on spleen cells seems to be controlled by the same genetic locus which determines the presence of Glx + gp70 on thymocytes. Our analysis of spleen-cell surfaces for expression of MuLV-gp70 molecules involved standard immunochemical methods. Spleen cells of 129, B6, and their congenic Gixand Glx + derivatives were surface-radioiodinated by the lactoperoxidase method and the cells lysed with detergents. A group-specific goat anti-

Abstract: The inborn errors of metabolism have played a special role in the development of human genetics as a scientific discipline. The study of these disorders, each of them individually uncommon, has pointed out the ways in which molecular expression of gene action takes place in man. It has given us new understanding of mechanisms of human variation. It has pioneered in the field of prenatal diagnosis and has permitted new approaches to questions of population genetics by permitting the detection of recessive genes in heterozygotes. Each of these aspects of modern biochemical genetics is exemplified by the inborn errors of purine metabolism, an area in which there have been exciting new developments.