Biology Reference
In-Depth Information
The alleles of closely linked polymorphisms often occur in specific combinations
or
haplotypes
. In the
-globin (
HBB
; 11p15) gene, for example, some haplotypes
have been identified in Europeans, Asians, Blacks, and Chinese, indicating that
their origin must have predated racial divergence (Antonarakis
et al
., 1985). By
contrast, other haplotypes are population-specific or 'private' (e.g. Schneider
et
al
., 1998; Wainscoat
et al
., 1986). In some cases, the number of different haplo-
types can be quite high, the result of the shuffling of different single base-pair
substitutions by such processes as recombination and gene conversion (Fullerton
et al
., 1994).
In their analysis of 8 kb of intronic sequence of the Duchenne muscular dys-
trophy (
DMD
; Xp21) genes of individuals from 13 different human populations
[European, Papua New Guinean, African (6), Asian (3) and Amerindian (2)],
Zietkiewicz
et al
. (1997) identified 36 polymorphisms. Of these, 15 were shared
among most of the populations screened, 13 were confined to Africans and four
were confined to non-Africans. A detailed study of human DNA polymorphism
has also been performed on a 9734 bp region of the human lipoprotein lipase
(
LPL
; 8p22) gene, comprising 8736 bp intronic sequence and 998 bp coding
sequence, performed on 142 chromosomes from 71 individuals from three dis-
tinct populations: Finns, European-Americans and African-Americans
(Nickerson
et al
., 1998). A total of 88 sites were found to vary (79 single base-pair
substitutions and nine microdeletions or microinsertions) representing an aver-
age of one variable site every 500 bp. Only seven of the 88 variable sites were
found in the coding region. At 34 of the 88 sites, the variation was found in only
one of the three populations reflecting the differing population and mutational
histories. A total of 88 unique haplotypes were identified in the 142 chromosomes
sampled, probably a reflection of the complex historical interplay of recombina-
tion and mutation. Finally, a study of a total of 87 kb of human chromosome Xq22
revealed 102 polymorphisms, seven of which were shared by Europeans,
Ashkenazim, and pygmies, two by pygmies and Europeans, and 19 by
Ashkenazim and Europeans (Anagnostopoulos
et al
., 1999).
Some polymorphisms within human gene coding regions also occur in the
orthologous genes of the great apes. In some cases, this may imply an origin for
the polymorphism that predated the adaptive radiation of the higher primates
('trans-species polymorphism'). Perhaps the best example of this phenomenon is
provided by the ABO blood group locus (
ABO
; 9q34.1-q34.2). In humans, there
are four amino acid substitutions (in positions 176, 235, 266 and 268) that distin-
guish the A- and B-transferases (respectively R, G, L, and G in A-transferase and
G, S, M, and A in B-transferase) whilst the O allele is characterized by a single
nucleotide (G
261
) frameshift deletion that inactivates the protein (Yamamoto
et al
.,
1990). The gorilla and chimpanzee possess types B and A respectively whilst the
baboon (
Papio cynocephalus
) exhibits both A and B (Yamamoto
et al
., 1990;
Kominato
et al
., 1992; Martinko
et al
., 1993). Certain alleles of the major histo-
compatibility complex (MHC) are also very ancient. Indeed, it would appear that
some of the class I MHC allelic lineages are shared by human, chimpanzee and
gorilla, implying that these polymorphisms were present in the common ancestor
of the three species (see Chapter 4, section 4.2.1,
Genes of the major histocompatibil-
ity complex
). Another possible example of trans-species polymorphism is to be
