Penrose and sib-pairs

Penrose's sib-pair papers (1935-1953) are discussed in relation to recent applications. His essential contribution that parental typing was an inefficient addition to sib-pair data for linkage detection remains. Parents now have even less to offer with contemporary markers in the detection of linkage, although not the enumeration of haplotypes. Attention is drawn to two little known papers by Penrose on multifactorial disease, and it is suggested that this term should replace polygenic in relation to family analyses. The convention established by Penrose, both as author and editor, of raw data being published alongside its analysis, which later fell into disuse on grounds of sheer bulk, can now be remedied by the Internet, and has been for the largest set of sib-pair data on diabetes (Davies et al. Nature 371 (1994), 130-136). This is essential if the contributions to the identity and location of alleles possibly relevant to common disorders, none of which are likely to be more than suggestive in any single study, can be combined to assess consistency and joint evidence. Attention is drawn to a third little known paper by Penrose of high relevance to the strategy of familial investigations in multifactorial disorders. All five of the Penrose papers discussed here can be viewed at http:/(/)www.gene.ucl.ac.uk/anhumgen/.