512 Paul Thompson
Other factors such as meiotic drive can be added either as additional parameters
in the Hardy-Weinberg equilibrium or as separate ratios or equations.
Against this background, a precise application of aX^2 -test of goodness of fit can
be provided. The following example^40 illustrates the determination the goodness
of fit between observed data and the expected data based on the Hardy-Weinberg
equilibrium. The human chemokine receptor^41 gene CC-CKR-5codes for a major
macrophage co-receptor for the human immunodeficiency virus HIV-1. CC-CKR-5
is part of the receptor structure that allows the entry of HIV-1 into macrophages
and T-cells. In rare individuals, a 32-base-pair indel^42 results in a non-functional
variant of CC-CKR-5. This variant of CC-CKR-5 has a 32-base-pair deletion
from the coding region. This results in a frame shift and truncation of the trans-
lated protein. The indel results when an individual is homozygous for the allele
∆32^43. These individuals are strongly resistant to HIV-1; the variant CC-CKR-5
co-receptor blocks the entry of the virus into macrophages and T-cells.
In a sample of Parisians studied for non-deletion and deletion (+ and ∆32
respectively), Lucotte and Mercier (1998) found the following genotypes:
++ : 224 + ∆32 : 64 ∆32∆32 : 6Dividing by the populations sample size yields the genotype frequencies:
++ : 224/294 = 0.762 + ∆32 : 64/294 = 0.218 ∆32∆32 : 6/994 = 0. 20Multiplying the number of homozygotes for an allele by 2 and adding the number
of heterozygotes yields the number of that allele in the sample. Dividing that by
(^40) The data is taken from Hartl [2000].
(^41) Immune responses depend on the activities of white blood cells (leukocytes). Some immune
responses are innate (i.e., one is born with them). These depend, to a large extent, on the action
of granulocytes of which macrophages are an instance. Some immune responses are adaptive (i.e.,
one develops the immunity in response to a pathogen). These depend on lymphocytes of which T
lymphocytes (or T-cells) are an instance. Macrophages and T-cells have on their surfaces highly
diverse receptors. These receptors can be stimulated to provoke an action or can be used to
bind to a pathogen. Sometimes binding to a pathogen is sufficient to block its entry into a cell
and, hence, neutralize it. Sometimes binding enables a phagocyte cell to ingest the pathogen.
And there are a large number of other mechanisms. A cytokine is a protein made by cells, that
activates a behaviour in another cell. A chemokine is a small cytokine, prinicipally involved
in the migration and activation of phagocytes and lymphocytes. The chemokine receptor on a
macrophage is the receptor through which chemokines stimulate the activity of the macrophage.
It is also the receptor that provides an entry point into the macrophage of HIV-1.
(^42) DNA in an intertwined helical ladder, the rungs of which consist of two connected nucleotides.
That is each rung is comprised of two joined nucleotides. There are four nucleotides in DNA:
adenine (A), guanine (G), thymine (T) and cytosine (C). the only possible combinations are C
and G, and A and T. So a segment of five rungs could be A-T, T-A, G-C, A-T, C-G. DNA
polymorphisms are ubiquitous in nature. That is, at a defined site in the DNA of an organism,
many different sequences of nucleotide pairs are present in different individuals (nucleotide poly-
morphism). An indel is an insertion or deletion polymorphism – a sequence of nucleotides are
added or deleted in some individuals creating a polymorphism at that site. A 32-base-pair indel
is an addition/deletion of 32 rungs of the DNA ladder.
(^43) The reference to ∆32 is a switch in reference points. CC-CKR-5 is a nucleotide sequence at
the molecular-genetic-level/DNA. ∆32 is an allele at the population-genetic-level/chromosomal
level. This allelic composition determines the DNA composition of the individual.