Genetics and human health

2.28 It is now common in reporting about health issues for BRCA1 and BRCA2 to be used as a form of shorthand for ‘breast cancer’. This is highly misleading: everyone has the BRCA1 and BRCA2 genes, which in their correct form have a role in suppressing the growth of tumours in breast and ovarian tissue. Increased risk of breast cancer is due to inheriting the mutated alleles of these genes (including from the father, it should be noted, contrary to popular myth), which removes their protective capacity.

2.29 Ridley has pointed out that the tendency to identify a specific gene as the cause of disease obscures the vital role of genes in human health:

Open any catalogue of the human genome and you will be confronted not with a list of human potentialities, but a list of diseases, mostly named after pairs of obscure central-European doctors. … The impression given is that genes are there to cause diseases. …

Yet to define genes by the diseases they cause is about as absurd as defining organs of the body by the diseases they get: livers are there to cause cirrhosis, hearts to cause heart attacks and brains to cause strokes. It is a measure, not of our knowledge but of our ignorance, that this is the way the genome catalogues read. It is literally true that the only thing we know about some genes is that their malfunction causes a particular disease. This is a pitifully small thing to know about a gene, and a terribly misleading one. It leads to the dangerous shorthand that runs as follows: ‘X has got the Wolf-Hirschhorn gene’. Wrong. We all have the Wolf-Hirschhorn gene, except, ironically, people who have Wolf-Hirschhorn syndrome. Their sickness is caused by the fact that the gene is missing altogether. In the rest of us the gene is a positive, not a negative force. The sufferers have the mutation, not the gene.[26]

2.30 Medical conditions or diseases linked to genes can be classified in a number of ways.[27] Importantly for this Inquiry these include:

  • Monogenic (or single gene) disorders;
  • Polygenic (or multi-gene) disorders; and
  • Multifactorial disorders.

2.31 In addition, there are chromosomal disorders (such as Down syndrome)[28] and somatic cell disorders (such as cancer), in which the genetic abnormality was not present at conception but was acquired during life and is found only in specific cells rather than in all cells in the body.[29]

2.32 Table 2–1, at the conclusion of this Chapter, lists a number of more common genetic disorders. The table describes the prevalence of the disorder, the mutations involved, the pattern of inheritance, the age of onset, and the opportunities for diagnosis, prevention and treatment.[30]

Monogenic disorders

2.33 A monogenic disorderis one in which a mutation in one or both alleles of a single gene is the main factor in causing a genetic disease. Much of our early understanding about genetic influences on health is derived from the observation and study of monogenic disorders such as HD. However, such diseases are relatively rare:

Huntington’s disease is at the far end of the spectrum of genetics. It is pure fatalism, undiluted by environmental variability. Good living, good medicine, healthy food, loving families or great riches can do nothing about [it]. Your fate is in your genes.[31]

2.34 The rarity of monogenic disorders is an important consideration in developing a policy framework for the protection of human genetic samples and information. Monogenic disorders allow relatively accurate inferences to be drawn about a person’s future health from their current genetic status. However, this is not the case with the vast majority of genetic disorders, where the relationship between genetic status and disease is highly complex and contingent.

Polygenic disorders and haplotyping

2.35 We are increasingly aware that the vast majority of medical conditions with some genetic link involve either the complex interaction of a number of genes (polygenic) or the complex interaction between genes and the environment (multifactorial disorders).[32] As Ridley has stated:

Unless you are unlucky enough to have a rare and serious genetic condition, and most of us do not, the impact of genes upon our lives is a gradual, partial, blended sort of thing. You are not tall or a dwarf, like Mendel’s pea plants, you are somewhere in between. You are not wrinkled or smooth, but somewhere in between. This comes as no great surprise, because just as we know it is unhelpful to think of water as a lot of little billiard balls called atoms, so it is unhelpful to think of our bodies as the products of single, discrete genes.[33]

2.36 According to the Human Genome Database,[34] as of 29 December 2002, 14,014 genes have been mapped to individual chromosomes, of which 1,639 have been identified as being involved in a genetic disorder. It may be that most of the simple linkages have already been made, since the rate of discovery has slowed dramatically despite better technology: of the last 3,783 genes to have been mapped, only 17 have been identified with a genetic disorder.

2.37 Following the success of the Human Genome Project, the ‘next big thing’, according to Dr Francis Collins, director of the United States National Human Genome Research Institute, is to produce a Human Haplotype Map. Haplotypes (or haplotype blocks) refer to a number of closely-linked alleles along a region of a chromosome, which tend to be inherited together.[35]

2.38 According to the US National Human Genome Research Institute:

The elucidation of the entire human genome has made possible our current effort to develop a haplotype map of the genome. The haplotype map, or ‘HapMap’, will be a reference work that catalogs the genetic variations of most importance to health and disease.

The DNA sequence of any two people is some 99.9 percent identical. The variations, however, may greatly affect an individual’s disease risk. Sites in the DNA sequence where individuals differ at a single DNA base are called single nucleotide polymorphisms (SNPs). Sets of nearby SNPs on the same chromosome are inherited in blocks. This pattern of SNPs on a block is a haplotype. Blocks may contain a large number of SNPs, but a relatively few SNPs can be enough to uniquely identify a haplotype. The HapMap is a map of these haplotype blocks, including the specific SNPs that identify the haplotypes.

The HapMap will enable researchers to quickly compare a patient’s genetic patterns with known patterns, and thus determine if that patient is at risk for particular diseases. In addition, people with the same disease may respond differently to the same drug treatments; the HapMap will enable researchers to examine drug efficacy in specific diseases with genetic patterns. Finally, haplotype mapping will reveal the role of variation in individual responses to environmental factors.[36]

2.39 In theory, there could be large numbers of haplotypes in a chromosome region; however, recent research suggests that there are a smaller number of common haplotypes—perhaps as few as four or five common patterns across all populations—which would permit researchers to shortcut their work dramatically by testing for genetic predispositions for such complex diseases as cancer, diabetes, hypertension, and Alzheimer’s block-by-block, rather than letter-by-letter.[37] Researchers involved in the work supporting this ‘common variant hypothesis’ have drawn three important conclusions:

First, the human genome can be objectively parsed into simple haplotype blocks each averaging 11,000 to 22,000 DNA letters but only four or five different variations in the letters. Second, the blocks are similar across individuals from Africa, Europe, and Asia, suggesting that a map of haplotypes will have broad utility for most people. Third, the haplotype blocks appear to capture about 90 percent of genetic variation in a region of the human genome.[38]

2.40 According to Mark Daly, one of the authors:

This study is a significant step toward developing a more powerful statistical approach to studying complex human disease. Genetics has not made tremendous inroads in complex disease, even though great effort has been put in during the last 10 to 15 years. As a community, we’ve come to understand that complex diseases are not caused by single high-penetrance genes, but from more modest risk factors common in populations.

This study provides a great deal of hard data scientists can use to go back and refine and improve models of population biology and molecular evolution. For once, genetics worked out to be easier than it could have been. But now we have to do the disease studies, which will not be simple.[39]

Multifactorial disorders and the environment

2.41 In the case of multifactorial disorders, inheriting a mutated allele for particular conditions means that the person is susceptible or predisposed to develop the condition. Other factors such as diet or exposure to certain environmental factors are necessary to ensure the expression of the trait or condition. Most of the important and common medical problems in humans are multifactorial, including heart disease, hypertension, psychiatric illness (such as schizophrenia), dementia, diabetes, and cancers.

2.42 For much of the latter part of the last century, the prevailing orthodoxy was that ‘nurture’ (environment) is far more important than ‘nature’ (genes) in influencing human development,[40] at least outside of the basic inherited physical traits. The pace and weight of genetic research in recent times, however, appears to have tipped common wisdom in the other direction—perhaps too far in the direction of genetic exceptionalism and determinism (see Chapter 3).

2.43 In fact, the picture is far more complex. A person is not the sum of a column of traits and behaviours determined by individual genes. Instead, it is better to think of a person as comprising all of the product of his or her genes; the intricate interaction of those genes; and the elaborate interaction between that genetic legacy and environmental factors.

2.44 Even a simple reference to ‘the environment’ understates the dynamic and multifaceted nature of this relationship. At the most simple level, the quality of the environment—a nutritious diet, access to good health care, opportunities for exercise—will allow the full expression of genetically inherited traits, such as height. Over a lifetime, other aspects of the physical environment also will shape human health and development—for example, air and water pollution, endemic disease, workplace safety, drought and war. Choice and chance also play an important role—smoking and skydiving pose dangers to health unrelated to genetic inheritance, and a high speed, head-on car accident will always trump good genes.

2.45 As Ridley has put it:

You had better get used to such indeterminacy. The more we delve into the genome the less fatalistic it will seem. Grey indeterminacy, variable causality and vague predisposition are the hallmarks of the system … because simplicity piled upon simplicity creates complexity. The genome is as complicated and indeterminate as ordinary life, because it is ordinary life. This should come as a relief. Simple determinism, whether of the genetic or environmental kind, is a depressing prospect for those with a fondness for free will.[41]

2.46 The environment is also full of social constructs that affect our well–being and the opportunities to reach our full potential. If a community prohibits women from receiving higher education or bars certain racial groups from employment through discrimination, then inherent intellectual ability will count for little. Similarly, if a community is pre-occupied with idealised (and atypical) body images, then this may contribute to severe eating disorders and ill health in otherwise healthy young women, notwithstanding genes that code for good health.

Diseaseor protective trait?

2.47 There is a tendency to label many genetic variations as ‘diseases’ or ‘disorders’—but historically, some of these mutations served to enhance the prospects of survival in certain environmental contexts. The following examples involve autosomal recessive conditions in which the genetic ‘abnormality’ does not cause significant clinical problems for the carrier (but would do so in a child who inherits affected genes from both parents).[42]

  • -thalassaemia is common in the Mediterranean area and in many parts of Southeast Asia. The genetic defect involves impairment in the synthesis of a protein (b-globin) found in red blood cells. The carrier state, present in as many as 1 in 10 people in some populations, affords protection against malaria because carriers have pale and small red blood cells that do not provide the malaria parasite with a good environment in which to grow. Carriers tend to have very mild anaemia (not enough to cause serious health problems) but the homozygous affected person has severe anaemia, which usually requires life-long blood transfusion.

  • Tay–Sachs disease (TSD) is ten times more common in the Ashkenazi (Central and eastern European) Jewish community than in non-Jews or Sephardic (Middle Eastern) Jews, resulting in a carrier frequency of about 1 in 30 people. It is a neurological degenerative disease that usually results in death by the age of four or five. Carriers of the mutated allele for TSD do not have any symptoms of the condition, but it is thought that the carrier state provided protection against tuberculosis in the cramped conditions of the ghettos in which the Jewish population had to live in times past.

  • Cystic fibrosis (CF) is common in many ethnic groups but particularly among Caucasians—about one in 25 of whom are carriers of the mutated allele for CF. The defect in CF involves movements of chloride across cells and causes severe problems in lung and pancreatic functions for those with the disease. Those people who are carriers of the mutated allele for CF do not move chloride (ie salt) across their membranes as well as those who are not carriers, and so are at less risk of dying from diarrhoea. Over the many thousands of years of evolution, this would have been a useful mutation to carry when cholera and dysentery were endemic. Carriers generally do not have the symptoms of CF (in fact carrier status only can be determined through a DNA test) but a child inheriting the CF mutated allele from both parents may develop severe health problems (although CF is very variable in its severity).

  • Sickle cell anaemia is caused by a mutation in the haemoglobin gene, and is common among persons from Africa and the Mediterranean area. The carrier state affords protection against malaria, however, because carriers have abnormal red blood cells that die soon after being infected with the malaria parasite, compared with normal red blood cells, which continue to work and to provide an environment in which the malaria parasite can grow. In an evolutionary sense, being a carrier for sickle cell disease is a good thing if one lives in a region in which there is endemic malaria.

2.48 The link between an individual’s genetic status and the expression of a genetic disorder, and the link between the expression of a disorder and particular health outcomes, are discussed in detail throughout this Report. In particular, the following chapter examines some of the difficulties in interpreting genetic information in a way that is reliable and relevant for the many contexts in which genetic information is or may be used, now and in the future.


[26] M Ridley, Genome: The Autobiography of a Species in 23 Chapters (1999) Fourth Estate, London, 54–55.

[27] R Trent, Molecular Medicine: An Introductory Text (2nd ed, 1997) Churchill Livingstone, 37.

[28] Ibid, 69–70.

[29] Ibid, 210–211.

[30] The inquiry thanks Associate Professor Eric Haan, a member of the Advisory Committee, for the preparation of this Table.

[31] M Ridley, Genome: The Autobiography of a Species in 23 Chapters (1999) Fourth Estate, London, 64.

[32] R Trent, Molecular Medicine: An Introductory Text (2nd ed, 1997) Churchill Livingstone, 55, 211.

[33] M Ridley, Genome: The Autobiography of a Species in 23 Chapters (1999) Fourth Estate, London, 66.

[34] An international collaboration in support of the Human Genome Project. See the excellent website hosted by the Hospital for Sick Children in Toronto, Canada, which contains regularly updated tables containing details of ‘Genetic Disorders by Chromosome’, as well as a ‘Display Map’ to view genetic disorders mapped to a chromosome. See Hospital for Sick Children, Reports and Statistics, <>, 18 February 2003.

[35] Haplotype and allele frequencies are affected by cellular-level processes as well as by population-level processes: National Human Genome Research Institute, Developing a Haplotype Map of the Human Genome for Finding Genes Related to Health and Disease, <
ID=10001665>, 20 February 2003.

[36] See the National Human Genome Research Institute website: Ibid.

[37] See S Gabriel and others, ‘The Structure of Haplotype Blocks in the Human Genome’ (2002) 296 Science 2225; discussed in C Morton, The Next Big Thing in Mining the Genome: A Simpler Tool for Finding Disease Genes and Spotting Genetic Variation, Harvard University Focus, <
2002/June7_2002/genomics.html>, 21 July 2002.

[38] C Morton, The Next Big Thing in Mining the Genome: A Simpler Tool for Finding Disease Genes and Spotting Genetic Variation, Harvard University Focus, <
genomics.html>, 21 July 2002. However, for a contrary view of the promise of haplotype research, see J Couzin, ‘New Mapping Project Splits the Community’ (2002) 296 Science 1391.

[39] C Morton, The Next Big Thing in Mining the Genome: A Simpler Tool for Finding Disease Genes and Spotting Genetic Variation, Harvard University Focus, <
genomics.html>, 21 July 2002.

[40] See S Rose, L Kamin and R Lewontin, Not in Our Genes: Biology, Ideology and Human Nature (1985) Pantheon.

[41] M Ridley, Genome: The Autobiography of a Species in 23 Chapters (1999) Fourth Estate, London, 75.

[42] Information provided by Advisory Committee members Professor Ron Trent and Dr Kristine Barlow-Stewart. See also R Trent, Molecular Medicine: An Introductory Text (2nd ed, 1997) Churchill Livingstone, 10–11.

[43] However, a man who is a carrier of a mutated allele and has a polymorphism in the other allele may not have outwards symptoms of CF, but may be infertile.