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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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Comparison with the physical and genetic maps of Trypanosoma brucei brucei. The genetic maps of T. b. brucei isolate TREU 927 and T. b. gambiense isolate STIB 386 are shown alongside the TREU 927 physical map of the same chromosome for (a) chromosome 1 and (b) chromosome 2. The average physical size of a recombination unit between each marker is given in kb/cM and the genetic distance given in cM. Dashed lines link the position of all markers on the physical map to their relative position on the genetic maps. Hot and cold spots are defined as threefold more or less recombination than average for each genetic map and indicated against the physical map by red and blue bars, respectively.
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Figure 4: Comparison with the physical and genetic maps of Trypanosoma brucei brucei. The genetic maps of T. b. brucei isolate TREU 927 and T. b. gambiense isolate STIB 386 are shown alongside the TREU 927 physical map of the same chromosome for (a) chromosome 1 and (b) chromosome 2. The average physical size of a recombination unit between each marker is given in kb/cM and the genetic distance given in cM. Dashed lines link the position of all markers on the physical map to their relative position on the genetic maps. Hot and cold spots are defined as threefold more or less recombination than average for each genetic map and indicated against the physical map by red and blue bars, respectively.

Mentions: Although the average rate of recombination in the T. b. gambiense map was found to be 24.4 kb/cM, there is variation both between and within the chromosomes, as is common in many other eukaryotic organisms [35]. A correlation of the physical and genetic sizes of every chromosome in the map is shown in Figure 3, and the average physical size of a recombination unit ranges from a high of 39 kb/cM on chromosome 11 to a low of 13 kb/cM on chromosome 5 (Table 1). Variation is also evident between specific intervals across chromosomes where a map unit can vary from under 1 kb/cM up to 170 kb/cM on the same chromosome (chromosome 11; Additional data file 2) representing extremes in recombination frequency. If we define hot and cold spots of recombination as three times less (cold) or three times more (hot) than the average recombination rate, the boundaries for defining hot and cold regions can be set at under 8 kb/cM and over 73 kb/cM, respectively, based on an average physical size of a recombination unit of 24 kb/cM. Analysis of crossovers in the STIB 386 × STIB 247 progeny revealed that variation in recombination frequency between markers is common, producing a least one hot or cold region on every chromosomes and a total of 15 hot and 27 cold spots overall (Figure 4 and Additional data file 2).


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)

Comparison with the physical and genetic maps of Trypanosoma brucei brucei. The genetic maps of T. b. brucei isolate TREU 927 and T. b. gambiense isolate STIB 386 are shown alongside the TREU 927 physical map of the same chromosome for (a) chromosome 1 and (b) chromosome 2. The average physical size of a recombination unit between each marker is given in kb/cM and the genetic distance given in cM. Dashed lines link the position of all markers on the physical map to their relative position on the genetic maps. Hot and cold spots are defined as threefold more or less recombination than average for each genetic map and indicated against the physical map by red and blue bars, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Comparison with the physical and genetic maps of Trypanosoma brucei brucei. The genetic maps of T. b. brucei isolate TREU 927 and T. b. gambiense isolate STIB 386 are shown alongside the TREU 927 physical map of the same chromosome for (a) chromosome 1 and (b) chromosome 2. The average physical size of a recombination unit between each marker is given in kb/cM and the genetic distance given in cM. Dashed lines link the position of all markers on the physical map to their relative position on the genetic maps. Hot and cold spots are defined as threefold more or less recombination than average for each genetic map and indicated against the physical map by red and blue bars, respectively.
Mentions: Although the average rate of recombination in the T. b. gambiense map was found to be 24.4 kb/cM, there is variation both between and within the chromosomes, as is common in many other eukaryotic organisms [35]. A correlation of the physical and genetic sizes of every chromosome in the map is shown in Figure 3, and the average physical size of a recombination unit ranges from a high of 39 kb/cM on chromosome 11 to a low of 13 kb/cM on chromosome 5 (Table 1). Variation is also evident between specific intervals across chromosomes where a map unit can vary from under 1 kb/cM up to 170 kb/cM on the same chromosome (chromosome 11; Additional data file 2) representing extremes in recombination frequency. If we define hot and cold spots of recombination as three times less (cold) or three times more (hot) than the average recombination rate, the boundaries for defining hot and cold regions can be set at under 8 kb/cM and over 73 kb/cM, respectively, based on an average physical size of a recombination unit of 24 kb/cM. Analysis of crossovers in the STIB 386 × STIB 247 progeny revealed that variation in recombination frequency between markers is common, producing a least one hot or cold region on every chromosomes and a total of 15 hot and 27 cold spots overall (Figure 4 and Additional data file 2).

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