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Biomedical subjects

M A Ferguson-Smith

Publications and source records attributed to M A Ferguson-Smith.

At least 19 recordsLinked to original sources
PubMed1992

Cytogenetic analysis by chromosome painting using DOP-PCR amplified flow-sorted chromosomes.

A novel polymerase chain reaction (PCR) technique has been combined with chromosome flow sorting to characterise two lymphoblastoid cell lines and one medullary thyroid carcinoma cell line carrying translocations close to the locus for multiple endocrine neoplasia type 2A (MEN 2A). Five hundred copies of the derivative chromosome(s) were flow sorted from each cell line and amplified by degenerate oligonucleotide-primed-polymerase chain reaction (DOP-PCR). This generated pools of DNA sequences corresponding to the abnormal chromosomes, which were then used as probes in fluorescence in situ hybridisation (FISH) experiments on normal metaphase cells. The resultant chromosome paints revealed the portions of the normal chromosomes related to those involved in the translocations. By this technique, translocation breakpoints in bands p15, q11.2, and q21 of chromosome 10 were defined in the above cell lines, in two cases refining previous cytogenetic data. This study shows that flow sorting of aberrant chromosomes and chromosome painting can be used as a rapid aid to cytogenetic analysis, particularly in cases of difficult karyotypes, such as tumours. Furthermore, the DOP-PCR technique described here will have applications to other areas of genome analysis, such as cloning of new markers; its design will allow a general and representative amplification to occur from any starting DNA in any species.

Cell Line↗
PubMed1992

A molecular deletion map of the Y chromosome long arm defining X and autosomal homologous regions and the localisation of the HYA locus to the proximal region of the Yq euchromatin.

41 Y-linked DNA probes that detect sequences on the Y chromosome long arm have been used to analyse genomic DNA from a series of 23 patients with deletions of Yq. Southern blot analysis has differentiated 15 distinct breakpoints, which divide Yq into 14 mapping intervals. From the pattern of DNA sequences present in each patient, it has been possible to produce a congruent deletion map, with the exception of two cases which are not compatible with the consensus order. These patients can be explained by the presence of inversion polymorphisms on Yq in the general population or by complex rearrangements induced during the formation of the deleted chromosomes. The distribution of sequences on the Y long arm has defined distinct regions of homology with autosomes, the Y short arm and the long and short arms of the X. A number of the patients have been typed for the presence or absence of H-Y antigen (as determined by the cytotoxic T-cell assay) and it has been possible, from analysis of informative cases, to assign the locus to the proximal region of the Yq euchromatin.

Cell Line↗
PubMed1979

Use of chromosomal translocations with in situ DNA hybridisation to confirm localisation of human 5S ribosomal RNA genes.

Two cases of chromosomal translocations involving the long arm of chromosome 1 were investigated for 5S ribosomal gene localisation using in situ hybridisation. In the first family, there was an interstitial translocation of 1q25-32 to chromosome 5; the 5S genes remained on chromosome 1. In the second family, there was a translocation of 1q42-44 to chromosome 21q12; the 5S gene locus in this case was translocated. This shows that the 5S ribosomal genes are at position 1q42-44, confirming a previous assignment based on adenovirus-induced uncoiling and on a partial trisomy (Steffensen et al., 1977).

Chromosome Banding↗
PubMed1978

Avoidance of anencephalic and spina bifida births by maternal serum-alphafetoprotein screening.

Screening of 11 585 pregnant women between 16 and 20 completed weeks' gestation for raised serum-alphafetoprotein (A.F.P.) levels showed that the birth of 81.4% of babies with open neural-tube defects could be avoided. The screening test was sensitive enough to detect 93% of those affected and serum-A.F.P. levels above the point at which intervention shouldbe considered were found in 1.7% of pregnancies. After 75.2% of false-positives had been excluded by ultrasonography or by a repeat of the serum test, only 0.63% of pregnancies proceeded to amniocentesis, 46.6% of amniocenteses showed raised amniotic A.F.P. levels due to fetal abnormality. Fetal loss by abortion or perinatal death after amniocentesis occurred in 0.034% of pregnancies screeded, 75% being associated with threatened abortion before amniocentesis. There were no terminations of normal pregnancies due to false-positive amniotic A.F.P. results. It is concluded that voluntary maternal serum-A.F.P. screening has a valuable role in antenatal care.

Amniocentesis↗
PubMed1978

The linkage relationships of marker sites on chromosomes no. 2 and 10.

Two families in which aberrations involving chromosome no. 2 had been previously used for linkage studies have been re-examined using banding techniques to identify the breakage sites. In one family a (2; 10)(q21;q24) translocation was identified in individuals previously thought to have a pericentric inversion of chromosome no. 2. In the other, a fragile secondary constriction site was localized to 2q13, and it was shown by bromodeoxy uridine incorporation that the origin of the triradial chromosome no. 2 was by isochromatid breakage and non-disjunction rather than by selective endoreduplication. The three marker sites, 2q13, 2q21 and 10q24, have been analysed for their linkage relationships with 15 informative marker loci which have not yet been assigned to chromosomes other than no. 2 or no. 10. No significant evidence for linkage with any of the loci tested was found.

Chromosome Banding↗
PubMed1978

Meiotic analysis of a pericentric inversion, inv(7) (p22q32), in the father of a child with a duplication-deletion of chromosome 7.

In a family in which a large pericentric inversion of chromosome 7 is segregating, two of the four progeny of inversion heterozygotes show severe psychomotor retardation and have the karyotype 46,XX,rec(7),dup q,inv(7)(p22q32), derived from crossing-over within the inversion. Meiotic analysis in one of the heterozygotes revealed no evidence of inversion loops in well-spread pachytene cells. In approximately 20% of cells in diakinesis, the presumptive bivalent 7 had only one chiasma. Two alternatives to the reversed loop mode of meiotic pairing of inversions are proposed. Review of the literature supports the view that "small" pericentric inversions have a much better genetic prognosis than "large" pericentric inversions.

Abnormalities, Multiple↗
PubMed1978

Meiotic studies in mice carrying the sex reversal (Sxr) factor.

A sex reversal factor (Sxr) that causes mice having apparently normal X chromosomes to become phenotypically male is transmitted in an autosomal pattern. The origin of the Sxr factor is still unknown. It seems most likely that it has originated from an autosomal gene mutation or is the result of a translocation of part of the Y chromosome to one of the autosomes. Chromosomes from four XY and six XO mice carrying this sex reversal factor were examined in the diakinesis stage of meiosis. The following unusual observations were noted: (1) in XY males carrying the Sxr factor, the X and Y chromosomes were separated more often than in controls. (2) The Y chromosome tends to be closer to an autosome when the X and Y are separate than when the X and Y are attached. (3) A chromosome fragment was present in 4/226 cells from two XO males and a single cell from an XY, Sxr carrier. Although there is no direct evidence, these observations seem to favor the possibility that the Sxr factor involves a chromosomal rearrangement rather than a single gene mutation.

Animals↗