Residential radon in Peru: challenges for health surveillance and lung cancer prevention.

The Journal of Genetics, started by William Bateson in 1910, played a distinguished role in the early years of genetics. However, it stopped publishing in 1978. The Indian Academy of Sciences revived it in 1985, and has published it regularly since then. To commemorate this landmark, I highlight one of the 17 articles published that year. 'The isolation and genetic analysis of a Caenorhabditis elegans… X-chromosome balancer' by András Fodor and Péter Deak, of the Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary. More than the 43 citations garnered by the article, including one as recently as 2023 (Genome Res. 33, 154-167, 2023), my choice was driven by my friendship with Péter Deak. We overlapped in our postdoctoral years. Additionally, András Fodor was a visiting scientist in TIFR, Mumbai, in 1979/80. What are balancers? Drosophila geneticists routinely use balancer chromosomes to suppress crossover. Balancers are chromosomes with inversions. Consider the diploid progenitor cell of eggs or sperm with one chromosome of normal sequence, and the other, its inversion homologue. Crossover in the 'heterozygous' segment generates chromosomes with complementary duplications and deletions of segments outside the inversion. These produce genic imbalances in the gametes and inviable progeny. Additionally, balancers are dominantly marked to easily identify individuals that bear them, and they carry one or more recessive lethal mutations to eliminate balancer-homozygotes, that might otherwise be indistinguishable from heterozygotes. Self-crosses versus out-crosses. Caenorhabditis elegans is a free-living soil nematode that feeds on bacteria. Individual nematodes are either self-fertilizing hermaphrodites or males. Both have five pairs of autosomes. Additionally, hermaphrodites have two X chromosomes (XX) but males only one (XO). Hermaphrodites produce both sperm and oocytes, and their fusion produces self-cross progeny. The fraction of heterozygous genome is halved in each successive self-cross. Males mate with hermaphrodites, and fertilization of eggs by male-derived sperm generates out-cross progeny. Isolation and analysis. Fodor and Deak crossed hermaphrodites homozygous for chr. X markers dpy-8 and unc-3 with males hemizygous for lon-2. F0 hermaphrodite progeny from the out-cross have a wild-type phenotype (WT). They were picked, mutagenized with X-rays, and allowed to self-cross. Individual WT hermaphrodite progeny (F1) were transferred to plates to produce self-cross lines (F2, F3, and F4). Most lines segregated the parental 'Lon' and 'Dpy Unc' type progeny as well as recombinant 'Dpy' and 'Unc' types. But one line (of 105) did not yield any recombinant types. It carried a newly induced X chromosome inversion (marked by lon-2) that suppressed crossover in the dpy-8-unc-3 interval. It was the balancer line. Surprisingly, the balancer line also did not yield any Lon hermaphrodites (lon-2 / lon-2 homozygotes), although it produced Lon males (lon-2 / O hemizygotes). This suggested the inversion was linked to a second rearrangement, a translocation, which additional crosses showed involved chromosome I. Thus, the balancer genotype was T(Xinv; I) lon-2. T(Xinv; I) lon-2 / T(Xinv; I) lon-2 hermaphrodites were inviable because of homozygosity for the chr. I breakpoint, whereas breakpoint-heterozygous I / T(Xinv; I) lon-2 / O males were viable because of heterozygosity for the breakpoint. The balancer was used in studies reported by Martin Chalfie, H. Robert Horvitz and John E. Sulston in Cell 24, 59-69, 1981. The Genome Res. 2023 article reported the balancer strain's genome sequence. It revealed a 280 kbp inversion on chr. X and a tightly linked (I; X) translocation. It pleases classical geneticists to see inferences made from genetic crosses being molecularly confirmed.