Minor chromosomal variants and major chromosomal anomalies in couples with recurrent abortion.

One hundred three women with prior histories of recurrent spontaneous abortion and 81 of their mates were karyotyped with Q-banding during 1976-1980. Recurrent abortion was defined as two or more spontaneous pregnancy losses; no couple with a previous malformed fetus or child was included. These cases were reviewed in order to examine the possible contributions of minor polymorphic chromosomal variants and major chromosomal abnormalities to recurrent spontaneous pregnancy loss. Balanced translocations were detected in four women and two men in the study; mosaic X aneuploidy was noted in one woman. Quantitative (1 qh, 9qh, 16qh, Yqh) and qualitative (3c, 4c, 13p, 13s, 14p, 14s, 15p, 15s, 21p, 21s, 22p, 22s) heterochromatic polymorphisms were blindly assessed and compared with a control group. Cases and controls did not differ in the frequency of any qualitative polymorphisms or in the length of any quantitative polymorphism. Thus, while major parental cytogenetic aberrations are significantly associated with fetal wastage, these data suggest that minor polymorphic chromosomal variants do not play an important role in the etiology of recurrent spontaneous abortion.

Assignment of the human gene for phosphoglycolate phosphatase to chromosome 16.

Seventeen independently derived primary mouse-human hybrid clones were scored for the expression of human phosphoglycolate phosphatase (PGP) by electrophoresis and for the presence of human chromosomes with the aid of Q banding. The correlation of biochemical and cytogenetic analyses shows that the segregation of human PGP in these hybrids is concordant only with human chromosome 16, thus enabling the assignment of the genetic locus for PGP to human chromosome 16.

Assignment of PGM3 to the long arm of human chromosome 6. Studies using Chinese hamster X human cell hybrids containing a human 6/15 translocation.

Hybrids derived from the fusion of thymidine kinase deficient Chinese hamster cells and human cells carrying a 6/15 translocation, 46,XX,t(6;15)(cen;p13), were analyzed for the expression of human PGM3, GLO and ME1. The results show that PGM3 and ME1 are on the long arm and GLO is on the short arm of human chromosomes 6.

Regional localization of human gene loci on chromosome 9: studies of somatic cell hybrids containing human translocations.

Somatic cell hybrids were derived from the fusion of (1) Chinese hamster cells deficient in hypoxanthine guanine phosphoribosyltransferase (HPRT) and human cells carrying an X/9 translocation and (2) Chinese hamster cells deficient in thymidine kinase (TK) and human cells carrying a 17/9 translocation. Several independent primary hybrid clones from these two series of cell hybrids were analyzed cytogenitically for human chromosome content and electrophoretically for the expression of human markers known to be on human chromosome 9. The results allow the assignment of the loci for the enzymes galactose-1-phosphate uridyltransferase (GALT), soluble aconitase (ACONs), and adenylate kinase-3 (AK3) to the short arm of chromosome 9 (p11 to pter) and the locus for the enzyme adenylate kinase-1 (AK1) to the distal end of the long arm of human chromosome 9 (hand q34). Earlier family studies have shown that the locus for AK1 is closely linked to the ABO blood group locus and to the locus of the nail-patella (Np) syndrome. Thus the regional localization of AK1 locus permits the localization of the AK1-Np-ABO linkage group.

Expression of galactose-1-p-uridyltransferase in Chinese hamster x human galactosemia somatic cell hybrids.

Lymphocytes from a patient with classic galactosemia (GALT deficiency) were hybridized with a Chinese hamster cell line. Electrophoretic valuation of GALT in 31 independently derived interspecific hybrid clones failed to demonstrate expression of the human GALT gene even when human chromosome 9 was present. Possible mechanisms for this lack of expression are presented.

Aconitase (E.C. 4.2.1.3) mitochondrial locus mapped to human chromosome 22: studies with Chinese hamster--human somatic cell hybrids.

Three separate somatic cell fusions were made between Chinese hamster lines and human lymphocytes containing (1) a 3/4 translocation, (2) an X/9 translocation, and (3) a 17/9 translocation. Eleven independently derived hybrids showed that only human chromosome 22 was consistently present when human ACONM was expressed and absent when human ACONM was not expressed. These studies assign a gene for human ACONM to chromosome 22, and are consistent with prior gene-mapping results.

Assignment of the human gene for galactose-1-phosphate uridyltransferase to chromosome 9: studies with Chinese hamster-human somatic cell hybrids.

Chinese hamster-human somatic cell hybrids were analyzed for the expression of human galactose-1-phosphate uridyltransferase (GALT; UDPglucose:alpha-D-galactose-1-phosphate uridyltransferase, EC 2.7.7.12) by electrophoresis and for the presence of human chromosomes cytogenetically with the aid of Q-banding. Three of the 10 randomly chosen independently derived primary hybrid lines showed the presence of human GALT. Human chromosome 9 was consistently present in the hybrid lines expressing human GALT and consistently absent in the lines not expressing it. Biochemical analysis alone of 11 independently derived hybrid lines showed human GALT to be syntenic with known chromosome 9 markers (soluble aconitase, adenylate kinase 1, and adenylate kinase 3). Previous studies on chromosome assignment of this locus, utilizing somatic cell hybrids, have yielded inconsistent results; one group assigned GALT to chromosome 2, and another assigned it to chromosome 3. However, we believe that, based on our results and other published evidence, the correct assignment of the human GALT locus is to chromosome 9.