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K O Simola

Publications and source records attributed to K O Simola.

25 records · Page 2Linked to original sources
PubMed1986

Localization of the LDHA gene to 11p14----11p15 by in situ hybridization of an LDHA cDNA probe to two translocations with breakpoints in 11p13.

Lymphoblastoid cell lines established from two individuals with apparently balanced translocations involving 11p13 were used for LDHA regional localization. The karyotypes were 46,XY,t(4;11)(q21;p13) and 46,XY,t(1;11)(p22;p13). In situ hybridization of a human LDHA cDNA probe to chromosome preparations from these cell lines resulted in specific labeling over bands p14----p15 of the normal chromosomes 11 and over bands 11p14----11p15 of the derivative chromosomes 4 and 1. These results exclude LDHA from any region proximal to 11p13 and localize the gene to 11p14----11p15.

Cell Line↗
PubMed1985

Segregation and fertility analysis in an autosomal reciprocal translocation, t(1;8)(q41;q23.1).

We report a previously undescribed autosomal reciprocal translocation, t(1;8)(q41;q23.1). It segregates in three families whose common origin lies at least 11 generations back. No examples of unbalanced karyotypes were encountered. Moreover, there was no circumstantial evidence that such live births had occurred during earlier generations. Couples in which one spouse was a translocation carrier were compared to related couples with normal karyotypes. The 15 carrier families had significantly more spontaneous abortions (32%) than the 22 normal couples (10%), irrespective of the sex of the carrier parent. However, the mean number of children was equal in both groups (2.0 and 2.4). Carrier families produced 17 children with a balanced translocation and seven with a normal karyotype. This deviates significantly (P = .04) from the expected 1:1 ratio. We conclude that this malsegregation helps to maintain the translocation in the population. These results show that empirically derived 1:1 segregation ratios previously reported in series that combine many different translocations do not apply to all individual translocations.

Abortion, Habitual↗
PubMed1983

Familial aniridia and translocation t(4;11)(q22;p13) without Wilms' tumor.

A family with dominantly inherited aniridia in three generations is presented. All three patients had an apparently balanced chromosome translocation t(4;11)(q22;p13). The patients were otherwise clinically normal and without signs of Wilms' tumor; their erythrocyte catalase activities were within the normal range. We suggest that in this family aniridia is caused either by a submicroscopic deletion at the translocation breakpoint 11p13 or by a position effect on the same chromosome segment. Furthermore, the loci for aniridia and Wilms' tumor susceptibility are separate. It follows that the WAGR complex is caused by a mutation of more than one gene located at 11p13. The theoretical implications of a presumably defective allele causing a mendelian dominant phenotype are discussed.

Chromosome Banding↗
PubMedDate not supplied

The beta-subunit of follicle-stimulating hormone is deleted in patients with aniridia and Wilms' tumour, allowing a further definition of the WAGR locus.

One in 10,000 children develops Wilms' tumour, an embryonal malignancy of the kidney. Although most Wilms' tumours are sporadic, a genetic predisposition is associated with aniridia, genito-urinary malformations and mental retardation (the WAGR syndrome). Patients with this syndrome typically exhibit constitutional deletions involving band p13 of one chromosome 11 homologue. It is likely that these deletions overlap a cluster of separate but closely linked genes that control the development of the kidney, iris and urogenital tract (the WAGR complex). A discrete aniridia locus, in particular, has been defined within this chromosomal segment by a reciprocal translocation, transmitted through three generations, which interrupts 11p13. In addition, the specific loss of chromosome 11p alleles in sporadic Wilms' tumours has been demonstrated, suggesting that the WAGR complex includes a recessive oncogene, analogous to the retinoblastoma locus on chromosome 13. In WAGR patients, the inherited 11p deletion is thought to represent the first of two events required for the initiation of a Wilms' tumour, as suggested by Knudson from epidemiological data. We have now isolated the deleted chromosomes 11 from four WAGR patients in hamster-human somatic cell hybrids, and have tested genomic DNA from the hybrids with chromosome 11-specific probes. We show that 4 of 31 markers are deleted in at least one patient, but that of these markers, only the gene encoding the beta-subunit of follicle-stimulating hormone (FSHB) is deleted in all four patients. Our results demonstrate close physical linkage between FSHB and the WAGR locus, suggest a gene order for the four deleted markers and exclude other markers tested from this region. In hybrids prepared from a balanced translocation carrier with familial aniridia, the four markers segregate into proximal and distal groups. The translocation breakpoint, which identifies the position of the aniridia gene on 11p, is immediately proximal to FSHB, in the interval between FSHB and the catalase gene.

Adult↗