Genetic difference: genotype and phenotype

2.12 All humans have the same basic set of about 32,000–35,000 genes, according to the latest best estimates.[15] This is far lower than the early estimates of 200,000, and even the relatively recent estimates of 100,000 used at the start of the Human Genome Project. This figure is similar for the mouse—and, at least for some people, uncomfortably close to the figures for the round worm (19,000), the fruit fly (13,000) and mustard cress (25,000). As has been widely reported, the human genome is more than 98% identical to that of chimpanzees, and 97% identical to that of gorillas.[16]

2.13 Genes may come in different versions, known as alleles. These alleles arise when there is a change in the ordering of the bases described above—in effect, a ‘typographical error’ in the code, involving the change of a single letter, the inversion of two letters, the deletion or insertion of a phrase (a ‘codon’), or the repetition of a phrase. This change in the sequence may cause no harm (a ‘polymorphism’), or it may make the gene faulty (a ‘mutation’) in the way it directs (expresses) the production of protein.

2.14 Although any two human beings will be 99.9% genetically identical, the precise DNA sequence of about 6.2 billion letters (3.1 billion base pairs) differs in each person’s genetic code. The remaining 0.1% of difference is thought to comprise more than 10 million common single-letter genetic variations (and a larger number of rare variants). The rate of variation is very low in humans (one single nucleotide polymorphism per 1300 bases) compared with other species, including other primates—suggesting a small species with a small ‘starter population’.[17]

2.15 These facts explain both the striking similarities among all people, which are the result of our common inheritance, and the many individual differences found even within a nuclear family.

2.16 Some genetic variations make little or no difference to health, for example hair colour. However, some mutations do affect basic functioning:

Mutations are permanent and inheritable changes in the ability of a gene to encode its protein. Much like typographical errors, which can change the meaning of a word, or even render a sentence as gibberish, such changes in gene structure can have severe effects on the ability of a gene to encode its protein. Some mutations prevent any protein from being produced, some produce a non-functional or only partially functional protein, and some produce a faulty or poisonous version of the protein.[18]

2.17 For example, Huntington’s disease (HD) is caused by a mutation to a gene that lies on chromosome 4, in which the triplet ‘CAG’ repeats an abnormally large number of times. Most people have 10–35 repeats; 40 or more repeats mean that the person will develop HD at some time, with a larger number of repeats leading to earlier and more severe onset. The complete lack of this triplet, together with other mutations, will cause another rare but serious disease, Wolf-Hirschhorn syndrome.[19]

2.18 The unique combination of alleles found in a particular individual’s genetic make-up is said to constitute that person’s genotype. The observable physical characteristics of this genotype, as determined by the interaction of both genetic makeup and environmental factors, is said to constitute that person’s phenotype. This includes such features as eye colour and hair colour, determined genetically,[20] as well as height and weight—determined by genetic factors as well as by diet and other environmental influences.

[15] E Lander, ‘Genomic Information: Driving a Revolution in Bio-Medicine’ (Paper presented at Seventh International Conference of the Human Genome Organisation, Shanghai, 14 April 2002).

[16] The principal genetic difference is that the other primates have 24 pairs of chromosomes, rather than the 23 pairs that characterise human beings This appears to be the result of the fusion of two medium-sized ape chromosomes to become human chromosome 2, the second largest of the human chromosomes. Human chromosome 2 is not only the same size as the two ape chromosomes put together, but it also contains the same pattern of bands: M Ridley, Genome: The Autobiography of a Species in 23 Chapters (1999) Fourth Estate, London, 24.

[17] E Lander, ‘Genomic Information: Driving a Revolution in Bio-Medicine’ (Paper presented at Seventh International Conference of the Human Genome Organisation, Shanghai, 14 April 2002).

[18] R Hawley and C Mori, The Human Genome: A User's Guide (1999) Harcourt Academic Press, Burlington, 6.

[19] M Ridley, Genome: The Autobiography of a Species in 23 Chapters (1999) Fourth Estate, London, 55.

[20] At least initially—hair colour and eye colour now can be modified cosmetically and, of course, hair colour can change naturally over time.