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Genetic analysis of the human infective trypanosome Trypanosoma brucei gambiense: chromosomal segregation, crossing over, and the construction of a genetic map.

Cooper A, Tait A, Sweeney L, Tweedie A, Morrison L, Turner CM, MacLeod A - Genome Biol. (2008)

Bottom Line: Forty-seven markers in this map were also used in a genetic map of the nonhuman infective T. b. brucei subspecies, permitting comparison of the two maps and showing that synteny is conserved between the two subspecies.The genetic linkage map presented here is the first available for the human-infective trypanosome T. b. gambiense.In combination with the genome sequence, this opens up the possibility of using genetic analysis to identify the loci responsible for T. b. gambiense specific traits such as human infectivity as well as comparative studies of parasite field populations.

View Article: PubMed Central - HTML - PubMed

Affiliation: Wellcome Centre for Molecular Parasitology, Glasgow Biomedical Research Centre, University Place, Glasgow G12 8TA, UK. acc15p@udcf.gla.ac.uk

ABSTRACT

Background: Trypanosoma brucei is the causative agent of human sleeping sickness and animal trypanosomiasis in sub-Saharan Africa, and it has been subdivided into three subspecies: Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, which cause sleeping sickness in humans, and the nonhuman infective Trypanosoma brucei brucei. T. b. gambiense is the most clinically relevant subspecies, being responsible for more than 90% of all trypanosomal disease in humans. The genome sequence is now available, and a Mendelian genetic system has been demonstrated in T. brucei, facilitating genetic analysis in this diploid protozoan parasite. As an essential step toward identifying loci that determine important traits in the human-infective subspecies, we report the construction of a high-resolution genetic map of the STIB 386 strain of T. b. gambiense.

Results: The genetic map was determined using 119 microsatellite markers assigned to the 11 megabase chromosomes. The total genetic map length of the linkage groups was 733.1 cM, covering a physical distance of 17.9 megabases with an average map unit size of 24 kilobases/cM. Forty-seven markers in this map were also used in a genetic map of the nonhuman infective T. b. brucei subspecies, permitting comparison of the two maps and showing that synteny is conserved between the two subspecies.

Conclusion: The genetic linkage map presented here is the first available for the human-infective trypanosome T. b. gambiense. In combination with the genome sequence, this opens up the possibility of using genetic analysis to identify the loci responsible for T. b. gambiense specific traits such as human infectivity as well as comparative studies of parasite field populations.

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Genotype segregation proportions. Genotype segregation proportions for all microsatellite markers present on chromosomes: (a) 2, (b) 3, (c) 4, (d) 5, (e) 6, (f) 7, (g) 8, (h) 9, (i) 10, and (j) 11. Dashed horizontal lines indicate the approximate 95% probability range for equal segregation of alleles.
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Figure 2: Genotype segregation proportions. Genotype segregation proportions for all microsatellite markers present on chromosomes: (a) 2, (b) 3, (c) 4, (d) 5, (e) 6, (f) 7, (g) 8, (h) 9, (i) 10, and (j) 11. Dashed horizontal lines indicate the approximate 95% probability range for equal segregation of alleles.

Mentions: The availability of segregation data across the length of each chromosome allows a full analysis of the inheritance of the STIB 386 parental chromosome homologs. The ratio of segregation of alleles for each heterozygous marker was calculated along each chromosome with the 95% confidence limits of a 1:1 segregation with 38 F1 progeny. This analysis had previously been conducted for the STIB 386 map of one of the smallest chromosomes, namely chromosome 1, and detected a region of significant distortion across the left arm of the chromosome [17]. Segregation analysis has now been performed on the remaining ten chromosomes (Figure 2) and this shows no evidence of distortion from a 1:1 segregation ratio across the length of chromosomes 4, 8, 9, or 10. On chromosomes 2, 5, 6, 7, and 11 there is one marker per chromosome, and on chromosome 3 there are two markers that have been inherited at proportions just outside the 95% confidence limits. However, it should be considered that this totals only seven out of 109 markers analyzed (6%), which is close to the 5% of outliers that would be expected with 95% confidence intervals and thus are unlikely to signify regions of true segregation distortion. Therefore, the previously reported region of chromosome 1 remains the only region of the STIB 386 genetic map for which there is evidence of any significant segregation distortion. The origin of this distortion is not known, but one possibility is that it is the result of postmeiotic selection acting on the uncloned progeny during growth in mice before isolation.


Genetic analysis of the human infective trypanosome Trypanosoma brucei gambiense: chromosomal segregation, crossing over, and the construction of a genetic map.

Cooper A, Tait A, Sweeney L, Tweedie A, Morrison L, Turner CM, MacLeod A - Genome Biol. (2008)

Genotype segregation proportions. Genotype segregation proportions for all microsatellite markers present on chromosomes: (a) 2, (b) 3, (c) 4, (d) 5, (e) 6, (f) 7, (g) 8, (h) 9, (i) 10, and (j) 11. Dashed horizontal lines indicate the approximate 95% probability range for equal segregation of alleles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2481433&req=5

Figure 2: Genotype segregation proportions. Genotype segregation proportions for all microsatellite markers present on chromosomes: (a) 2, (b) 3, (c) 4, (d) 5, (e) 6, (f) 7, (g) 8, (h) 9, (i) 10, and (j) 11. Dashed horizontal lines indicate the approximate 95% probability range for equal segregation of alleles.
Mentions: The availability of segregation data across the length of each chromosome allows a full analysis of the inheritance of the STIB 386 parental chromosome homologs. The ratio of segregation of alleles for each heterozygous marker was calculated along each chromosome with the 95% confidence limits of a 1:1 segregation with 38 F1 progeny. This analysis had previously been conducted for the STIB 386 map of one of the smallest chromosomes, namely chromosome 1, and detected a region of significant distortion across the left arm of the chromosome [17]. Segregation analysis has now been performed on the remaining ten chromosomes (Figure 2) and this shows no evidence of distortion from a 1:1 segregation ratio across the length of chromosomes 4, 8, 9, or 10. On chromosomes 2, 5, 6, 7, and 11 there is one marker per chromosome, and on chromosome 3 there are two markers that have been inherited at proportions just outside the 95% confidence limits. However, it should be considered that this totals only seven out of 109 markers analyzed (6%), which is close to the 5% of outliers that would be expected with 95% confidence intervals and thus are unlikely to signify regions of true segregation distortion. Therefore, the previously reported region of chromosome 1 remains the only region of the STIB 386 genetic map for which there is evidence of any significant segregation distortion. The origin of this distortion is not known, but one possibility is that it is the result of postmeiotic selection acting on the uncloned progeny during growth in mice before isolation.

Bottom Line: Forty-seven markers in this map were also used in a genetic map of the nonhuman infective T. b. brucei subspecies, permitting comparison of the two maps and showing that synteny is conserved between the two subspecies.The genetic linkage map presented here is the first available for the human-infective trypanosome T. b. gambiense.In combination with the genome sequence, this opens up the possibility of using genetic analysis to identify the loci responsible for T. b. gambiense specific traits such as human infectivity as well as comparative studies of parasite field populations.

View Article: PubMed Central - HTML - PubMed

Affiliation: Wellcome Centre for Molecular Parasitology, Glasgow Biomedical Research Centre, University Place, Glasgow G12 8TA, UK. acc15p@udcf.gla.ac.uk

ABSTRACT

Background: Trypanosoma brucei is the causative agent of human sleeping sickness and animal trypanosomiasis in sub-Saharan Africa, and it has been subdivided into three subspecies: Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, which cause sleeping sickness in humans, and the nonhuman infective Trypanosoma brucei brucei. T. b. gambiense is the most clinically relevant subspecies, being responsible for more than 90% of all trypanosomal disease in humans. The genome sequence is now available, and a Mendelian genetic system has been demonstrated in T. brucei, facilitating genetic analysis in this diploid protozoan parasite. As an essential step toward identifying loci that determine important traits in the human-infective subspecies, we report the construction of a high-resolution genetic map of the STIB 386 strain of T. b. gambiense.

Results: The genetic map was determined using 119 microsatellite markers assigned to the 11 megabase chromosomes. The total genetic map length of the linkage groups was 733.1 cM, covering a physical distance of 17.9 megabases with an average map unit size of 24 kilobases/cM. Forty-seven markers in this map were also used in a genetic map of the nonhuman infective T. b. brucei subspecies, permitting comparison of the two maps and showing that synteny is conserved between the two subspecies.

Conclusion: The genetic linkage map presented here is the first available for the human-infective trypanosome T. b. gambiense. In combination with the genome sequence, this opens up the possibility of using genetic analysis to identify the loci responsible for T. b. gambiense specific traits such as human infectivity as well as comparative studies of parasite field populations.

Show MeSH
Related in: MedlinePlus