A deletion mutation in GDF9 in sisters with spontaneous DZ twins.

A loss of function mutation in growth differentiation factor 9 (GDF9) in sheep causes increased ovulation rate and infertility in a dosage-sensitive manner. Spontaneous dizygotic (DZ) twinning in the human is under genetic control and women with a history of DZ twinning have an increased incidence of multiple follicle growth and multiple ovulation. We sequenced the GDF9 coding region in DNA samples from 20 women with DZ twins and identified a four-base pair deletion in GDF9 in two sisters with twins from one family. We screened a further 429 families and did not find the loss of function mutation in any other families. We genotyped eight single nucleotide polymorphisms across the GDF9 locus in 379 families with two sisters who have both given birth to spontaneous DZ twins (1527 individuals) and 226 triad families with mothers of twins and their parents (723 individuals). Using case control analysis and the transmission disequilibrium test we found no evidence for association between common variants in GDF9 and twinning in the families. We conclude that rare mutations in GDF9 may influence twinning, but twinning frequency is not associated with common variation in GDF9.     

The structure of a small collagenous fragment isolated from chicken hyaline cartilage

In previous experiments, two collagenous fragments were isolated from pepsin digests of chicken hyaline cartilage and called the high molecular weight, (HMW) and low molecular weight (LMW) fractions [3]. In the present experiments, the chains of LMW were isolated after denaturation and subsequent reduction and alkylation of interchain disulfide bridges and were further fractionated by carboxymethyl-cellulose chromatography. Four peaks were resolved during chromatography and were designated LMW 1, 2A, 2B, and 3. Amino acid analyses and peptide mapping after cleavage with trypsin, V8 protease, and cyanogen bromide showed that three genetically distinct chains must be present in LMW. Fractions 2A and 2B were very similar, but not identical, in structure. LMW 1, 2A plus 2B, and 3 were consistently isolated in approximately equal proportions, suggesting that the probable chain organization of LMW is [1][2A + 2B][3]. This suggestion was supported further by experiments that attempted to fractionate LMW by carboxymethyl-cellulose chromatography after denaturation but without reduction and alkylation of interchain disulfide bridges. No fractionation of LMW was achieved, the single peak subsequently being shown to contain LMW 1, 2A plus 2B, and 3.     

The ultraviolet sensitivity of Cockayne syndrome cells is not a consequence of reduced cellular NAD content

Cells from individuals with Cockayne syndrome (CS) are hypersensitive to the lethal effects of ultraviolet light (uv) and show a number of abnormal biochemical responses following uv-irradiation. Fujiwara et al. recently reported that the NAD contents of CS fibroblasts were lower than those of normal fibroblasts, and that addition of NAD to the cellular growth medium rectified most of the abnormal responses of CS cells to uv-irradiation. In our experiments, however, the cellular NAD contents of normal and CS fibroblasts were similar, and addition of NAD to the growth medium had no effect on the hypersensitivity of CS cells to uv-irradiation, nor did it restore the inability of CS cells to recover normal rates of DNA or RNA synthesis following uv-irradiation.