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Biomedical subjects

W Amos

Publications and source records attributed to W Amos.

At least 19 recordsLinked to original sources
PubMed2003

Unravelling dispersal patterns in an expanding population of a highly mobile seabird, the northern fulmar (Fulmarus glacialis).

The northern fulmar (Fulmarus glacialis) is an abundant seabird whose Northeast Atlantic population has expanded dramatically over the past 100 years. Archaeological evidence suggests that Iceland and St Kilda were the ancestral populations from which essentially all other colonies in the region were derived. We collected samples from seven breeding colonies around the North Atlantic and used mitochondrial DNA analysis to ask whether population structure was present and, if so, where there was evidence about which colony was the dominant source population. Our data reveal a pattern consistent with isolation by distance, suggesting that, even though capable of flying great distances, most birds return to breed either at their own or neighbouring colonies. Interestingly, although most colonizers appear to have come originally from Iceland, our analysis also identifies St Kilda as a possible source. However, this secondary pattern appears to be largely an artefact, and can be attributed to the low haplotype diversity on St Kilda which yields a much clearer isolation by distance signal than that generated by birds dispersing from Iceland, where haplotype diversity is extremely high. Consequently, we urge caution when interpreting patterns in which populations vary greatly in the genetic diversity they harbour.

Animals↗
PubMed2001

The influence of parental relatedness on reproductive success.

The relationship between fitness and parental similarity has been dominated by studies of how inbreeding depression lowers fecundity in incestuous matings. A widespread implicit assumption is that adult fitness (reproduction) of individuals born to parents who are not unusually closely related is more or less equal. Examination of three long-lived vertebrates, the long-finned pilot whale, the grey seal and the wandering albatross reveals significant negative relationships between parental similarity and genetic estimates of reproductive success. This effect could, in principle, be driven by a small number of low quality, inbred individuals. However, when the data are partitioned into individuals with above average and below average parental similarity, we find no evidence that the slopes differ, suggesting that the effect is more or less similar across the full range of parental similarity values. Our results thus uncover a selective pressure that favours not only inbreeding avoidance, but also the selection of maximally dissimilar mates.

Animals↗
PubMed2001

Reproductive performance links to fine-scale spatial patterns of female grey seal relatedness.

Fine-scale spatial patterns of female relatedness throughout the established grey seal breeding colony of North Rona, Scotland, were investigated by accurate mapping and spatially explicit analyses of a large sample (n = 262) of mothers using variation at nine microsatellite DNA loci. Local spatial autocorrelation analyses identified locations where seals were more highly related to the colony than average. These locations were also areas where the more successful females bred, were occupied first during each breeding season, were centrally placed locations of preferred habitat types and were likely to be the locations which were the first to be colonized historically. Mothers occupying such sites achieved higher than average pup growth rates, suggesting a founder fitness benefit.

Animals↗
PubMed2001

When does conservation genetics matter?

Is this short review we explore the genetic threats facing declining populations, focusing in particular on empirical studies and the emerging questions they raise. At face value, the two primary threats are slow erosion of genetic variability by drift and short-term lowering of fitness owing to inbreeding depression, of which the latter appears the more potent force. However, the picture is not this simple. Populations that have passed through a severe bottleneck can show a markedly reduced ability to respond to change, particularly in the face of novel challenges. At the same time, several recent studies reveal subtle ways in which species are able to retain more useful genetic variability than they 'should', for example by enhanced reproductive success among the most outbred individuals in a population. Such findings call into question the validity of simple models based on random mating, and emphasize the need for more empirical data aimed at elucidating precisely what happens in natural populations.

Adaptation, Biological↗
PubMed2001

Low reproductive success in territorial male Antarctic fur seals (Arctocephalus gazella) suggests the existence of alternative mating strategies.

Microsatellites were used to conduct an analysis of paternity of Antarctic fur seals (Arctocephalus gazella) from Bird Island, South Georgia. At most, only 28% of pups at our study site could be assigned a father, even though the majority (approximately 90%) of candidate males within this colony were sampled. The behavioural and genetic evidence from this study suggests that a number of alternative mating strategies may exist within this fur seal population. Holding a land-based territory conferred an advantage to male reproductive success. However, this advantage was much smaller than expected from behavioural observations. At least 70% of fur seal pups born at our study site in a given year are not fathered by males who held a territory or were observed copulating with females in the previous year, implying that there exists a pool of males that seldom venture ashore at this site. To explain this discrepancy we suggest that female choice is an integral component of the Antarctic fur seal mating system and that aquatic mating may play a much larger role in the Antarctic fur seal than previously thought.

Animals↗
PubMed2001

Maladaptive mate choice maintained by heterozygote advantage.

Common buzzards (Buteo buteo) show a plumage polymorphism that appears to be maintained by heterozygote advantage and allows a maladaptive form of mate choice to persist. The light and dark morphs have a much lower fitness than the presumed heterozygous intermediate morph, but are replenished through Mendelian segregation in intermediate-intermediate pairs. Light and dark morphs could maximize their fitness by mating light with dark to produce all intermediate offspring, but instead choose partners of their own color, thereby producing broods of minimally fit homozygotes. Such maladaptive behavior argues forcefully against mate choice based on "good genes," and its persistence is best explained by heterozygote advantage maintaining the polymorphism coupled with nongenetic mate choice based on sexual imprinting. Modeling different patterns of mate choice shows that random mating and preference for own morph fit our data poorly, whereas preference for mother's morph yields a good fit.

Animals↗
PubMed2000

Y-chromosomal diversity in Europe is clinal and influenced primarily by geography, rather than by language.

Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.

Africa, Northern↗
PubMed2000

Genetic susceptibility to tuberculosis in Africans: a genome-wide scan.

Human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis. We have conducted a two-stage genome-wide linkage study to search for regions of the human genome containing tuberculosis-susceptibility genes. This approach uses sibpair families that contain two full siblings who have both been affected by clinical tuberculosis. For any chromosomal region containing a major tuberculosis-susceptibility gene, affected sibpairs inherit the same parental alleles more often than expected by chance. In the first round of the screen, 299 highly informative genetic markers, spanning the entire human genome, were typed in 92 sibpairs from The Gambia and South Africa. Seven chromosomal regions that showed provisional evidence of coinheritance with clinical tuberculosis were identified. To identify whether any of these regions contained a potential tuberculosis-susceptibility gene, 22 markers from these regions were genotyped in a second set of 81 sibpairs from the same countries. Markers on chromosomes 15q and Xq showed suggestive evidence of linkage (lod = 2.00 and 1.77, respectively) to tuberculosis. The potential identification of susceptibility loci on both chromosomes 15q and Xq was supported by an independent analysis designated common ancestry using microsatellite mapping. These results indicate that genome-wide linkage analysis can contribute to the mapping and identification of major genes for multifactorial infectious diseases of humans. An X chromosome susceptibility gene may contribute to the excess of males with tuberculosis observed in many different populations.

Adolescent↗
PubMed2000

Conditional ETDT analysis of the human leukocyte antigen region in type 1 diabetes.

Several studies have indicated that additional genes in the major histocompatibility complex (MHC) region, other than the class II genes HLA-DQB1 and -DRB1 (the IDDM1 locus), may contribute to susceptibility and resistance to type 1 diabetes. The relative magnitude of these non- DR/DQ effects is uncertain and their map location is unknown owing to the extraordinary linkage disequilibrium that extends over the 3.5 Mb of the MHC. The homozygous parent test has been proposed as a method for detection of additional risk factors conditional on HLA-DQB1 and -DRB1. However, this method is inefficient since it uses only parents homozygous for the primary disease locus, the DQB1-DRB1 haplotype. To overcome this limitation, Conditional ETDT was used in the present report to test for association conditional on the DQB1-DRB1 haplotype, thereby allowing all parents to be included in the analysis. First, we confirm in UK and Sardinian type 1 diabetic families that allelic variation at HLA-DRB1 has a very significant effect on the association of DQB1 and vice versa. The Conditional ETDT was then applied to the HLA TNF (tumour necrosis factor) region and microsatellite marker D6S273 region, both of which have been reported to contribute to IDDM1 independent of the HLA-DQB1-DRB1 genes. We found no evidence for a major role for either of these two regions in IDDM1.

Adolescent↗
PubMed2000

Patterns of paternal relatedness in British grey seal colonies.

Previous studies of breeding behaviour in the grey seal, Halichoerus grypus, have painted conflicting pictures. Behavioural observations suggest a classical polygynous system with a small number of dominant males fathering most of the offspring. However, genetic analysis suggests that many potential fathers spend little time ashore, that some pairs of seals show partner fidelity and that the dominant males are not as successful as their behaviour would suggest. Here we used paternal relatedness between pups with known mothers, sampled over an 11-year period, to show that behavioural dominance leading to enhanced fitness is a feature of only a handful of males located near the centre of the breeding colony. The vast majority of pups are fathered by any of a large number of males who all share approximately equal success, including virtually all those males who have previously escaped our best sampling efforts. As expected, the frequency of full-sibs is reduced in this longer time series relative to the original study. However, absolute estimates of the frequency of full-sibs seem to be confounded by a tendency for females who produce paternally unrelated pups to have conceived to males who are more genetically dissimilar from each other than expected by chance alone. Together, these elements of breeding behaviour would help to maintain maximum genetic diversity and to minimize the effects of inbreeding.

Animals↗
PubMed2000

Population structure of long-finned pilot whales in the North Atlantic: a correlation with sea surface temperature?

The long-finned pilot whale, Globicephala melas, is a social, pelagic odontocete distributed widely in the cold temperate waters of the North Atlantic. Despite genetic, morphometric, physiological and observational studies, it remains unclear whether any population substructure exists. We have used eight highly polymorphic microsatellite loci to analyse samples from four disparate sampling sites: USA East Coast (Cape Cod), West Greenland, the Faeroe Islands and the UK. Our results indicate that substructure does exist, and is particularly pronounced between West Greenland and other sites. The magnitudes of the various pairwise comparisons do not support a simple isolation-by-distance model. Instead, the patterns of genetic differentiation suggest that population isolation occurs between areas of the ocean which differ in sea surface temperature. Such a mechanism is supported by the observation that temperature is a primary factor determining the relative distributions of two short-finned pilot whale (G. macrorhynchus) populations off the Pacific coast of Japan.

Animals↗
PubMed1999

Markov chain Monte Carlo analysis of human Y-chromosome microsatellites provides evidence of biased mutation.

We describe a Markov Chain Monte Carlo analysis of five human Y- chromosome microsatellite polymorphisms based on samples from five diverse populations. Our analysis provides strong evidence for mutational bias favoring increase in length at all loci. Estimates of population coalescent times and population size from our two largest samples, one African and one European, suggest that the African population is older but smaller and that the English East Anglian population has undergone significant expansion, being larger but younger. We conclude that Markov Chain Monte Carlo analysis of microsatellite haplotypes can uncover information not apparent when the microsatellites are considered independently. Incorporation of population size as a variable should allow us to estimate the timing and magnitude of major historical population trends.

Algorithms↗
PubMed1999

Where have all the fathers gone? An extensive microsatellite analysis of paternity in the grey seal (Halichoerus grypus).

Microsatellites were used to conduct an extensive analysis of paternity of grey seals from two Scottish breeding colonies at North Rona (n = 1189) and the Isle of May (n = 694), spanning more than a decade. A maximum of 46% of pups at North Rona and 29% of pups at the Isle of May could be allocated a father, even though the majority of candidate males for specific study sites within each colony were believed to have been sampled. Based on the paternities which could be assigned, both colonies showed evidence of reproductive skew, apparently due to the presence of approximately five males who were exceptionally successful. Some males were assigned paternities at least 10 years before, and colleagues 10 years after, being sampled, implying a reproductive lifespan of at least 10 years, and there are indications that the real maximum lies in the range 15-20 years. Male grey seals appear to have at least two breeding strategies they can adopt. On land, some males benefit from a traditionally polygynous system. However, between 50 and 70% of grey seal pups born at a particular colony are not fathered by males who are likely to be sampled by us, implying that these males seldom venture ashore here. We conclude that aquatic mating may play a much larger role in the grey seal than has previously been thought.

Animals↗
PubMed1999

Mitochondrial genetic analyses suggest selection against maternal lineages in bipolar affective disorder.

Previous reports of preferential transmission of bipolar affective disorder (BP) from the maternal versus the paternal lines in families suggested that this disorder may be caused by mitochondrial DNA mutations. We have sequenced the mitochondrial genome in 25 BP patients with family histories of psychiatric disorder that suggest matrilineal inheritance. No polymorphism identified more than once in this sequencing showed any significant association with BP in association studies using 94 cases and 94 controls. To determine whether our BP sample showed evidence of selection against the maternal lineage, we determined genetic distances between all possible pairwise comparisons within the BP and control groups, based on multilocus mitochondrial polymorphism haplotypes. These analyses revealed fewer closely related haplotypes in the BP group than in the matched control group, suggesting selection against maternal lineages in this disease. Such selection is compatible with recurrent mitochondrial mutations, which are associated with slightly decreased fitness. Although such mismatch distribution comparisons have been used previously for analyses of population histories, this is, as far as we are aware, the first report of this method being used to study disease.

Alleles↗
PubMed1999

An empirical exploration of the (delta mu)2 genetic distance for 213 human microsatellite markers.

Microsatellites are now used ubiquitously as genetic markers. One important application is to the assessment of population subdivision and phylogenetic relatedness. Such applications require a method of estimation of genetic distance. Here we examine the most widely used measure of microsatellite genetic distance, Goldstein et al.'s delta-mu squared ([delta mu]2), with respect to a large data set of 213 markers typed across samples from four diverse human populations. We find that (delta mu)2 yields plausible interpopulation distances. For the first time, we report significant interpopulation differences in mean microsatellite length, although the effect of these differences on (delta mu)2 is negligible. However, we also show that the method is extremely sensitive to one or two loci that contribute extreme values, even when a sample size of >200 loci is used. Some of these extreme loci can be removed on the grounds that some alleles carry large indels, but for others there is no clear justification for exclusion a priori. Our data suggest a rather recent African/non-African split, with an upper limit of some 70,000-80,000 years ago.

Africa↗
PubMed1998

Factors affecting levels of genetic diversity in natural populations.

Genetic variability is the clay of evolution, providing the base material on which adaptation and speciation depend. It is often assumed that most interspecific differences in variability are due primarily to population size effects, with bottlenecked populations carrying less variability than those of stable size. However, we show that population bottlenecks are unlikely to be the only factor, even in classic case studies such as the northern elephant seal and the cheetah, where genetic polymorphism is virtually absent. Instead, we suggest that the low levels of variability observed in endangered populations are more likely to result from a combination of publication biases, which tend to inflate the level of variability which is considered 'normal', and inbreeding effects, which may hasten loss of variability due to drift. To account for species with large population sizes but low variability we advance three hypotheses. First, it is known that certain metapopulation structures can result in effective population sizes far below the census size. Second, there is increasing evidence that heterozygous sites mutate more frequently than equivalent homozygous sites, plausibly because mismatch repair between homologous chromosomes during meiosis provides extra opportunities to mutate. Such a mechanism would undermine the simple relationship between heterozygosity and effective population size. Third, the fact that related species that differ greatly in variability implies that large amounts of variability can be gained or lost rapidly. We argue that such cases are best explained by rapid loss through a genome-wide selective sweep, and suggest a mechanism by which this could come about, based on forced changes to a control gene inducing coevolution in the genes it controls. Our model, based on meiotic drive in mammals, but easily extended to other systems, would tend to facilitate population isolation by generating molecular incompatabilities. Circumstances can even be envisioned in which the process could provide intrinsic impetus to speciation.

Animals↗