A.E. Retief

The gonads of human true hermaphrodites

SummaryGonadal distribution in 409 cases of human true hermaphroditism is reviewed. An ovary was found on the left side of the body in 62.8% of the cases and the testis on the right side in 59.5%. The ovotestis is the most common gonad of the true hermaphrodite; amongst 806 gonads in 406 cases it was found in 44.3%. In this paper we give a detailed description of the morphology of ovotestis, testis and ovary in the true hermaphrodite. In addition we discuss the effects of fetal androgens and Müllerian inhibitiing factor on the Wolffian and Müllerian ducts. Correlations between chromosomal complement and gonadal distribution are presented. True hermaphrodites with a 46,XX karyotype most commonly have an ovary on one side and an ovotestis on the other side; those with a Y-chromosome have a testis in 61% of cases. An analysis of the ratio of ovarian and testicular tissue within ovotestes showed a continuum from very little ovarian tissue to a small portíon of testicular tissue. Each type of tissue was clearly demarcated. Hypotheses for gonadal induction in the true hermaphrodite should take cognizance of these facts. True hermaprodites with a 46,XX chromosomal complement were characterized by a male phenotype in 54% of cases. This group may suggest a greater testicular induction ability in the genome as compared to the 46% with a female phenotype.

Chromosome changes in 17 human neoplasms studied with banding.

Chromosome abnormalities from 17 malignancies that were studied using direct preparations and G‐, Q‐, and C‐banding methods are presented and the findings assessed. The material used was from 6 primary cervical carcinomas, 5 primary and metastatic ovarian carcinomas and 6 other metastatic carcinomas. In general, chromosome 1 was found to be involved more frequently than the others in structural aberrations. These included short arm deletions—the most frequent marker over all the cases—long arm deletions, long arm duplications and various translocations including more complex rearrangements involving different breakpoints. Altogether ten common markers were identified among the cases, of which two were shared between two cervical carcinomas and two more, between a pair of ovarian carcinomas. The evidence in this report is in agreement with the finding of widespread involvement of chromosome 1 in malignancy, but with a particular preponderance in ovarian carcinoma.

CHROMOSOME STUDIES IN 496 INFERTILE MALES WITH A SPERM COUNT BELOW 10 MILLION/ML

SummaryChromosome studies were performed on 106 men with azoospermia and 390 men with oligozoospermia (consistant sperm count below 10 million/ml). Constitutional chromosome abnormalities were found in 14.1% of the azoospermia group and in 5.1% of the oligozoospermia group. An overall incidence of 7.1% constitutional abnormalities indicates that this criterion of selection may be advisable for routine chromosome analysis of infertile men. A reduction of 25% in the workload increases the yield of chromosome abnormalities in the group of infertile men to 10–14 times above that expected in the normal population.

The molecular basis and diagnosis of familial hypercholesterolaemia in South African Afrikaners

Three different point mutations were recently identified in South African familial hypercholesterolaemics. These mutations result in the modification of recognition sites of specific restriction endonucleases. This study describes rapid methods for presymptomatic detection of these defects based on restriction enzyme analysis or allele‐specific hybridization of enzymatically amplified genomic DNA. These methods were used to determine the frequencies of the three known low‐density lipoprotein (LDL) receptor gene mutations in 138 chromosomes of Afrikaner FH patients. It has been shown that a common mutation at the 3′ end of exon 4 (base 681) of the LDL receptor gene is present in about 70% of alleles, while the mutations in exons 9 (base 1285) and 4 (base 523) of the gene are present in about 20 and 10% respectively of the genes studied. These mutations were found in approximately 95% of Afrikaner familial hypercholesterolaemic patients studied, indicating at least three founder members for the disease in this population of South Arica.

The CEPH consortium primary linkage map of human chromosome 10

The first CEPH consortium map, that of chromosome 10, is presented. This primary linkage map contains 28 continuously linked loci defined by genotypes generated from CEPH family DNAs with 37 probe and enzyme combinations. Cytogenetic localization of some of the genetic markers indicates that the consortium map extends, at least, from 10p13 to 10q26. The order of loci on the consortium map agrees with the physical localization data. The female map spans 309 cM (206 cM if an approximation of interference is included in the mapping function used to construct the map), and the mean genetic distance of intervals is 11 cM (7 cM). Also presented are maps of chromosome 10 from each of five CEPH collaborating laboratories, based on genotypes for all relevant markers in the CEPH database. The CEPH consortium map of chromosome 10 should be useful for localization of any gene of interest falling within the span covered. The genotypes in the chromosome 10 consortium map database are now available to the scientific community.

Regional chromosome mapping of human collagen genes alpha 2(I) and alpha 1(I) (COLIA2 and COLIA1)

SummaryFor the assignment of the genes for the pro-α2(I) (COLIA2) and the pro-α1(I) (COLIA1) collagens, cDNA and genomic DNA probes were used in in situ hybridization experiments on human prometaphase chromosomes. An improved staining method is reported for the simultaneous identification of chromosomes and the autoradiographic grains after the hybridization procedures. With this procedure more cells with higher resolution could be used for the assignment of genes by in situ hybridization. Statistical analysis of the grains located on respectively 660 and 302 metaphases using pro-α2(I) and proα1(I) DNA probes, confirmed the assignment of these genes to human chromosomes 7 and 17. Analysis of the grain distribution on prometaphase chromosomes showed that the location of the proα2(I) collagen gene is in the region 7q21.3–22.1. The location of the pro-α1(I) collagen gene was found to be in band 17q21.31–2005.

Detection of a frequent polymorphism in exon 10 of the low-density lipoprotein receptor gene

SummaryDNA sequencing of enzymatically-amplified exons of the low-density lipoprotein receptor gene from several individuals revealed a polymorphism in exon 10 of the gene. The codon for arginine 450 was converted from AGG to AGA in some alleles.

No marker (X) syndrome in autistic children.

1Genetic Services, Department of Health and Welfare, Private Bag X63, Pretoria 0001, Republic of South Africa 2 Department Human Genetics, University of Orange Free State, Bloemfontein 9301, Republic of South Africa 3 New Hope School, Pretoria 0002, Republic of South Africa 4Department Cytogenetics, Tygerberg Hospital and Medical School, University of Stellenbosch, Tygerberg 7505, Republic of South Africa

Haplotype associations of three DNA polymorphisms at the human low density lipoprotein receptor gene locus in familial hypercholesterolaemia.

The frequency and inheritance of three restriction fragment length polymorphisms (RFLPs) of the low density lipoprotein (LDL) receptor gene were investigated in 27 South African families with familial hypercholesterolaemia. Four haplotypes, defined by the enzymes PvuII, StuI, and NcoI, were found to segregate in this population. The frequency of the rare allele detected by NcoI was found to be 0.53 in 45 unrelated familial hypercholesterolaemic (FH) patients compared to 0.33 in 60 normal controls (p less than 0.005). In 71% of the families studied, a haplotype with common alleles for PvuII and StuI and the rare allele for NcoI cosegregated with the defective gene. In 20% of the families, a second haplotype with rare alleles for PvuII and StuI and common allele for NcoI segregated with FH. In these families the haplotypes unambiguously cosegregate with the disease and can therefore be used for early diagnosis of FH.

Regional localization of α-galactosidase (GLA) to Xpter → q22, hexosaminidase B (HEXB) to 5q13 → qter, and arylsulfatase B (ARSB) to 5pter → q13

Two series of somatic cell hybrids were made by fusion of human cells with karyotypes 46,X,t(X;2;15)(q22;p12;p12) and 46,XX,t(5;7)(q13;p15) and rodent cells. Chromosome and isozyme analysis of human chromosomes and gene products in the hybrids localized GLA to Xpter----q22, HEXB to 5q13----qter, in both cases narrowing the regional assignments, and ARSB to 5pter----q13.