313 We term sleep a death. See Beckman and Ames (1998) and Ames et al. (1993) for a review of the free radical theory of ageing. See Rose (1991) for SOD in gerontocratic flies. Parkes et al. (1998) for overexpression of superoxide dismutase in Drosophila motorneurons; Finch and Ruvkun (2001) for a general review of SOD and ageing.
316 Our genomes contain three genes. Familial amyotrophic lateral sclerosis or ALS1 (105400) is caused by dominant mutations in Cu/Zn superoxide dismutase or SOD1 (147450) (Rosen et al. 1993). Deleting this gene in mice seems to have little obvious phenotypic effect, although longevity does not seem to have been examined (Reaume et al. 1996). For the experiments excluding free radicals and hydrogen peroxide as a cause of ALS see Subramaniam et al. (2002); for a review, Orr (2002). For a more general discussion on the causes of ALS see Newbery and Abbott (2002). For the role of SOD1 in Down’s syndrome see Epstein et al. (1987) and Reeves et al. (2001).
319 Wrinkling is a manifestation. Werner’s syndrome (277700) caused by recessive mutations in RECQL2 (also known as WRN) helicase (604611) (Yu et al. 1989) reviewed by Martin and Oshima (2000).
319 As we age. For two reviews of the proposed role of cellular senesence (or Hayflick’s limit) in ageing see Rose (1991) pp.126–36 and Shay and Wright (2000). Bodnar et al. (1997) show that overexpression of telomerase in human cell lines confers cellular immortality. There are some reports that the neuronal cells of mice do not undergo cellular senesence in vitro (Tang et al. 2001; Mathon et al. 2001). There are also strong suggestions that the proliferation of mouse cells in vitro is not telomere limited (Shay and Wright 2000).
321 Mice, it seems, can get by without telomerase. See Blasco et al. (1997), Lee et al. (1998) and Rudolph et al. (1999) for telomerase-deficient mice. One worry about these results is that laboratory mice seem to have much longer telomeres than wild mice (Weinstein and Ciszek, 2002).
322 One way to prove the point would be to clone a human. The original report on cloning Dolly was Wilmut et al. (1997). She died on 14 February 2003. Shiels et al. (1999) reported Dolly’s short telomeres. Cloned cattle appear to have perfectly normal, indeed rather long, telomeres (Lanza et al. 2000; Betts et al. 2001). There is a controversy about the healthiness of cloned animals (Cibelli et al. 2002; Wilmut, 2002). Six generations of mice have been cloned with no sign of rapid ageing – but then, they do seem to have very long telomeres.
323 Telomerase-mutant humans. Hutchinson-Gilford syndrome (progeria)(176670) is caused by a mutation in the gene encoding Lamin A and C.
323 In the last ten years there has been a revolution. See Kenyon et al. (1993) for a pioneering paper in C. elegans ageing studies, and Leroi (2001), Finch and Ruvkun (2001) and Partridge and Gems (2002) for recent reviews.
326 One of the first longevity genes to be identified. Alzheimer’s disease (104300). Late onset (AD2) is associated with particular polymorphisms in the apolipoprotein E gene (107741). For the relative risk of the ?4 allele see Corder et al. (1993); for its rarity in French centenarians see Schächter et al. (1994) and Charlesworth (1996).
327 All this seems to matter less if you are black. For the worldwide distribution of APOE alleles and discussion of relative risk of Alzheimer’s among ethnic groups see Fullerton et al. (2000). There are two ideas why Africans may not feel the deleterious effects of the ?4 allele. First, haplotype analysis shows that their ?4 alleles are somewhat different from those in European populations. Perhaps it simply lacks the pathogenic effect. Second, perhaps it has exactly the same effect, but Africans have, at high frequency, a variant at another locus that protects them against ?4. There is no reason to favour one idea over the other. For African APOE allele frequencies see Zekraoui et al. (1997).
327 In Europeans, at least, the genetics of Alzheimer’s provide. The early onset Alzheimer’s genes are: AD1, ?APP (104760); AD3, Presenilin 1 (104311) and AD4, Presenilin 2 (600759) (Charlesworth 1996).
327 These kinds of findings are only the beginning. Heijmans et al. (2000) review the state of the centenarian gene hunt.
329 In 1994 a remarkable thing happened. Much of the discussion on late-life mortality trends is based on Wilmoth (2000) and Wilmoth et al. (2000).
CHAPTER X: ANTHROPOMETAMORPHOSIS
335 The authors of books. Steve Jones, in the concluding chapter of his The language of the genes (1993) HarperCollins, London gives a classic Utopian account of humanity’s future. Mark Ridley, in the concluding chapter of his Mendel’s demon (2000) Weidenfeld and Nicolson, London suggests the wacky, but interesting, idea that we might evolve huge genomes and fantastically complex life-cycles. For the ethical views of some of the less inhibited scientists see the writings of Richard Dawkins and the late William Hamilton; for the opposition see the New York Review of Books (New York) and the Sunday Times (London).
337 Race has long been under siege. Steve Jones gives a good, if dated, account of these issues in The language of the genes. More recently, see Barbujani et al. (1997) and Rosenburg et al. (2002) for studies based on microsatellite loci; and Stephens et al. (2001) for single nucleotide polymorphisms.
339 The variants are known as AIMS. For an account of the search for AIMS see Collins-Schramm et al. (2002) and Shriver et al. (2003). For an account of the molecular genetics of FY (also known as Duffy) see Li et al (1997).
340 Skull measuring has a long history. See Bindman (2002) pp.201–21 for Camper on skull measurement (from which the quotes as well).
340 Sadly, Camper’s iconography. See Gould (1981) for the classic debunking work on craniometry and IQ. See Lahr (1996), Hanihara (2002) and Hennessy and Stringer (2002) for recent major craniometric studies, all of which build on the work of Bill Howells.
341 Human skulls are wonderfully diverse. See Lahr (1996) for an authoritative treatment of recent human skull diversity. The relative prognathism of Eskimos and Australian Aborigines is calculated from Hanihara (2002) Table 3.
342 My claim that we will soon be able. Boas published several studies on his immigrant data set, the most important of which was Boas (1912). The Rose quote is from Boyd (1955) p.299. Two recent papers, Sparks and Jantz (2002) and Gravlee et al. (2003), have reanalysed Boas’s data. The analysis done by each is somewhat different and they draw somewhat different conclusions. Sparks and Jantz (2002), however, do the critical analysis of variance – with ancestry, birthplace and their interaction as the effects. They show that there is a significant effect of birthplace and – just as one would expect from Boas’s hypothesis – a strong interaction effect. Contrary to Boas, however, the plasticity is small compared to the persistence of ancestral effects and the interactions are not of the sort that would necessarily cause skull shape to converge. They do not accuse Boas of fraud, but one cannot help but suspect that he presented those results that favoured his hypothesis and ignored those that did not. Gould (1981) p.108 cites Boas with approval.