The classical genetic picture of the genome was that most organisms, at any given gene locus, are homozygous for a single dominant allele, whose phenotype corresponds to the "wild type" norm for the species, and which is shared with other typical members of the same species. The occasional, rare phenotypic variant was believed to arise as a mutation, the large majority of which were regarded as recessive and deleterious. For example, most Drosophila have red eyes: the rare white-eyed fly was regarded as a mutant ("changed") that arose as a result of a mutation ("change") in a gene.
In humans, many easily-recognized single-gene traits result in medical conditions such as albinism (absence of skin pigment), polydactyly (extra digits), achondroplasia (stunted limb growth), etc., all of which we tend to put in the category of "diseases". Thus we tend to think of these rare individuals as "mutants" and therefore "abnormal," in contrast to the majority of the population who are (like ourselves) "normal". We tend to associate genetic variation with disease, and view all "mutation" as negative. These perceptions are inaccurate. Advances in molecular biology since the late 1960s have shown instead an enormous amount of genetic variation in most species, including our own. At the level of DNA sequences, it is likely that almost everyone is heterozygous at most gene loci, and (except for close relatives) is likely to differ from other members of the population. This being the case, the concept of a standard 'wild type' has no meaning. The basis of observed genetic differences are single-nucleotide polymorphisms (SNPs), alternative base pair differences at particular positions in the gene sequence. The variable effect of such SNP variation on phenotypes is one of the topics of this course. It remains the case that many gene variants do lead to medically deleterious conditions, and a great deal of time, money, and research is invested to understand and ameliorate such conditions.
In modern usage, we avoid the use of 'mutant' to refer to individual humans ("Queen Victoria was a mutant!"), though we may talk about 'mutant flies'. We also restrict the term 'mutation' to describe the molecular process by which gene variants are produced ("PKU results from a mutation of the PAH locus"), or to characterize a newly-arisen sequence variant ("a splice-site mutation"). DNA mutation gives rise to SNP variation within populations, however observed SNP differences between any two individuals likely arose long ago in their ancestors, rather than as a result of mutation in the parental generation. The exceptions are genetic variants observed in close relatives, which can often be traced to a particular mutational event in a common ancestor.
unconscious acceptance of inaccurate
attitudes about "What is Normal" with respect to genetic
variation have led to misinformed social
policy, sometimes with disastrous consequences. The term "eugenics"
was introduced in the late 19th century to describe efforts to
the human species by encouraging breeding of persons with "good
as evidenced by superior intelligence, general health, proper
status or skin
In the absence of any knowledge of genetics, early "positive
of livestock breeding, e.g.,
persons of 'good stock' should breed with
others like themselves and hope for the best.
With the rediscovery of Mendel's work on inheritance in peas, many scientists assumed that variation for almost any trait could be explained by single-gene Mendelian inheritance. For example, the US Navy in 1919 commissioned a study by the Eugenics Records Office of the genetics of "leadership ability" and "love of the sea" (thallasophilia), so as to provide a means of selecting naval cadets on the basis of their favourable pedigrees. Not surprisingly, 'leadership' was found to be dominant and 'sea lust' recessive and sex-limited, like beard growth (ever see a lady Admiral?). Textbooks showed pedigrees of the JS Bach family to demonstrate inheritance of musical ability, as shown by his multiple talented offspring. State fairs awarded blue-ribbons to 'fitter families' with sturdy, healthy children, presenting them with ribbons and medals in exactly the same way as superior livestock. Such efforts confuse heredity with familiality, the tendency of family members to resemble each other because of their shared environmental background. For example, boys often follow their fathers into military careers, the Bach children received music lessons from Dad, etc..
unfortunately had its dark side. For example, the
casualties of World War I were seen in some Western countries as
officers and soldiers killed tended to be young,
physically fit, pre-reproductive
males of superior intelligence, leaving behind those unqualified
military service to do the breeding. Studies of certain notorious 'feeble-minded' and/or
'criminal' families (notably,
the Kallikaks) concluded that such traits ran in
families, again ignoring effects of familial poverty,
social stigmatization ('Kallikak'
children were habitually shunned). The popularity of eugenic thinking
reinforced post-war anti-immigrant sentiment in the US: low IQ scores
immigrants were ascribed
to their poor
genetics, disregarding the fact that the tests were administered
English to non-English-speaking persons. It also led to efforts to
or actively interfere with the breeding of persons perceived to
have "bad genes".
and '30s, many US states and Canadian provinces passed laws
thousands of persons with a variety of conditions considered
on the basis of little or no evidence (epilepsy, mental
pauperism, etc). The Nazi regime in Germany
adopted these same laws, and extended them to outright murder of
institutionalized persons ("Lebensunwertes
of Life") in its Aktion T4
of the 1930s. Technical methods of large-scale execution
extended directly to the murder of millions in the Holocaust
J Cornwell, "Hitler's Scientists: Science, War, and the Devil's Pact"
C Browning, "The Origin of the Holocaust"
SJ Gould "The Mismeasure of Man," 2nd ed.