Yutaka Nakahori

The Y Chromosome Region Essential for Spermatogenesis

We analyzed DNA from 153 Japanese men with azoospermia or severe oligozoospermia whose Y chromosomes were cytogenetically normal. A total of 23 loci on the Y chromosome were examined: 15 loci within interval 6 including YRRM1 and DAZ, and 8 loci outside interval 6. Microdeletions were observed in 20 individuals. All deletions involved at least one locus within interval 6. The YRRM1 gene deletion was found in 4 patients, of whom 2 also lacked the SMCY gene. The remaining 16 individuals shared the absence of 10 loci between DYS7C and DYS239 including the DAZ gene. Among them, 13 were azoospermic while 3 showed a little sperm production, indicating that the common deletion resulted in phenotypic diversity. Since there is no region commonly deleted in all patients, azoospermia caused by deletion of the Y chromosome long arm may be genetically heterogeneous.

A minute deletion of the Y chromosome in men with azoospermia.

We analyzed deoxyribonucleic acid from 50 Japanese men with azoospermia whose Y chromosomes were cytogenetically normal. A total of 26 loci was examined in each patient. Of these patients 6 had small interstitial deletions, each of which was located within the distal part of Yq11. Five of these 6 patients lacked the same 2 loci, DYS7C and DYS1, while 1 patient had a larger deletion including DYS7C but not DYS1. More than 10% of all men with azoospermia of unknown origin may have minute interstitial deletions of the Y chromosome surrounding the DYS7C locus. The proximal part of this zone presumably encompasses the gene deletion that causes azoospermia.

New DNA polymorphisms of human MMH/OGG1 gene : prevalence of one polymorphism among lung-adenocarcinoma patients in Japanese

MMH/OGG1 is an 8-hydroxyguanine-specific DNA glycosylase/AP-lyase, one of the mutator enzymes for the excision repair of 8-hydroxyguanine. DNA polymorphisms in human MMH/OGG1 gene were newly identified and analyzed to examine a possible association with lung-cancer risk by a population-based study. Polymorphic allele 3 in hMMH/OGG1 exon 1 was significantly prevalent among Japanese patients with adenocarcinoma of the lung [odds ratio (OR): 3.152, 95% confidence interval (CI): 1.266-7.845], indicating that the excision repair of 8-hydroxyguanine may play a role in predisposition to lung cancer.

DNA analyses of XX and XX-hypospadiac males

Fourteen 46,XX “males” were analyzed by Southern blot hybridization with seventeen different Y chromosome-derived DNA probes and by the polymerase chain reaction for an additional two sites on the short arm of Y. Eight 46,XX males possessed various segments of the short arm of the Y chromosome, including the sex determining region. The detected segments ranged from the two most distal loci to nearly the entire length of the short arm, viz., 10 out of 11 loci. None of the eight patients had hypospadia. Five out of the six remaining cases had hypospadia and no Y sequence was detected, suggesting the presence of a causative difference between hypospadiac and non-hypospadiac groups.

PCR detection of structurally abnormal Y chromosomes.

SummaryThree probes each detecting a locus on the proximal long arm of the Y chromosome were partially sequenced. Thus, 3 sets of novel primers were developed which enable PCR detection of these 3 loci. Five previously reported primer sets, 3 on the short arm and each one on the centromere and the distal long arm, were mapped along with the novel three using a mapping panel consisted of 8 patients each with different structural abnormality of the Y chromosome. Now, PCR detection of these 8 loci covering an entire length of the Y chromosome has become possible enabling rapid screening of patients with Y chromosome aberrations.

Coarctation of the aorta and renal hypoplasia in a boy with Turner/Noonan surface anomalies and a 46,XY karyotype: A clinical model for the possible impairment of a putative lymphogenic gene(s) for Turner somatic stigmata

This paper describes a 12-year-old Japanese boy with coarctation of the aorta, renal hypoplasia, Turner/Noonan surface anomalies, and a 46,XY karyotype. Although the patient might represent an exceptional case of Noonan syndrome, the combination of the somatic stigmata appears to be consistent with a mutation of the putative lymphogenic gene(s) for Turner somatic stigmata.

A Y-associated allele is shared among a few ethnic groups of Asia.

SummaryIn our previous study, both of Y-associated alleles, Y1 and Y2, were detected in Japanese and Koreans, but only the Y1 allele was detected in each of other populations including Chinese in both Beijin and Guangzhou areas, Caucasians, Africans, and Jewish. In the present study, these observations were extended to other ethnic groups in East Asia. Evenks in central Siberia and Khalkhs in Mongolia had only the Y1 allele. On the other hand, two ethnic groups, Fo-lo and Hakka, in Taiwan had both of the Y1 and the Y2 alleles. Three of the eight Y2-positive men, 2 Fo-lo and a Hakka, shared family name Chen. Both Hakka people and ancesters of Chen families could be traced to the Province of Henan in northern China in early 4th century. They arrive din Fujian/Guangdong area in the south-east China via various routes and then some of them migrated to Taiwan in the 18th century. It is tempting to speculate that the Y2 allele may be originated from an ancestral population in Henan from which, Japanese, Koreans, and some of the Taiwanese diverged.

THE AZOOSPERMIC FACTOR ON THE Y CHROMOSOME

Azoospermia is the most frequent cause of male infertility. After excluding the obvious urological reasons and the effect of Klinefelters syndrome, azoospermia may be caused by an abnormality in the crucial gene(s) expressed during male germ cell differentiation. Recently, two candidate genes for azoospermia have been cloned from the azoospermic factor (AZF) locus on the Y chromosome long arm (Yq). One is YRRM (Y chromosome RNA recognition motif) gene, and the other is DAZ (deletion in azoospermia) gene. Both genes encode RNA binding protein and their expression is restricted to the testis. Therefore they are good candidates for AZF, although their function remains unclear. Here, the genes on the Y chromosome possibly involved in spermatogenesis and the role of the Y chromosome in evolution are discussed.

Pericentric inversion with a minute deletion of the Y chromosome in a severely oligozoospermic man.

An apparent pericentric inversion of the Y chromosome in a severely oligozoospermic infertile patient is described. The karyotype was 46,X,inv (Y) (p11.2 q11.23). DNA analysis, however, revealed a deletion involving nine loci within the most distal part of the euchromatic region of the long arm.

Refinement of the locus for X-linked recessive chondrodysplasia punctata

Although the locus for X-linked recessive chondrodysplasia punctata (CDPX1) has been mapped to the region between PABX and DXS31 (the critical region is about 3 Mb long), the precise location within the critical region has not been determined. In this paper, we describe a boy with a 46,Y,der(X)t(X;Y)(p22.3;q11)mat karyotype and review the genotype-phenotype correlations in three male patients with the combination of apparent lack of clinical features of CDPX1 and a partial deletion of the critical region. The results suggest that the region defined by the two BssHII sites at 3180 and 3570 kb from the Xp telomere may be the target region for the CDPX1 locus.