@article {771,
	title = {An expectation maximization approach to estimate malaria haplotype frequencies in multiply infected children.},
	journal = {Stat Appl Genet Mol Biol},
	volume = {6},
	year = {2007},
	month = {2007},
	pages = {Article33},
	abstract = {Characterizing genetic variability in the human pathogenic Plasmodium species, the group of parasites that cause Malaria, may have broad global health implications. Specifically, discerning the combinations of mutations that lead to viable parasites and the population level frequencies of these clonal sequences will allow for targeted vaccine development and individualized treatment choices. This presents an analytical challenge, however, since haplotypic phase (i.e. the alignment of bases on a single DNA strand) is generally unobservable in multiply infected individuals. This manuscript describes an expectation maximization (EM) approach to maximum likelihood estimation of haplotype frequencies in this missing data setting. The approach is applied to a cohort of N=341 malaria infected children in Uganda, Cameroon and Sudan to characterize regional differences. A simulation study is also presented to characterize method performance and assess sensitivity to distributional assumptions.},
	keywords = {Animals, Child, Gene Frequency, Genotype, Humans, Likelihood Functions, Malaria, Malaria Vaccines, Mutation, Plasmodium},
	issn = {1544-6115},
	doi = {10.2202/1544-6115.1321},
	author = {Li, Xiaohong and Foulkes, Andrea S and Yucel, Recai M and Rich, Stephen M}
}
@article {777,
	title = {Sequence diversity and evolution of the malaria vaccine candidate merozoite surface protein-1 (MSP-1) of Plasmodium falciparum.},
	journal = {Gene},
	volume = {304},
	year = {2003},
	month = {2003 Jan 30},
	pages = {65-75},
	abstract = {The merozoite surface protein-1 (MSP-1) of the malaria parasite Plasmodium falciparum is a major blood-stage antigen containing highly polymorphic tripeptide repeats in the domain known as block 2 and several non-repetitive domains that are essentially dimorphic. We have analyzed sequence variation in block 2 repeats and in non-repetitive block 17, as well as other polymorphisms within the MSP-1 gene, in clinical isolates of P. falciparum. Repeat haplotypes were defined as unique combinations of repeat motifs within block 2, whereas block 17 haplotypes were defined as unique combinations of single nucleotide replacements in this domain. A new block 17 haplotype, E-TNG-L, was found in one isolate from Vietnam. MSP-1 alleles, defined as unique combinations of haplotypes in blocks 2 and 17 and other polymorphisms within the molecule, were characterized in 60 isolates from hypoendemic Brazil and 37 isolates from mesoendemic Vietnam. Extensive diversity has been created in block 2 and elsewhere in the molecule, while maintaining significant linkage disequilibrium between polymorphisms across the non-telomeric MSP-1 locus separated by a map distance of more than 4 kb, suggesting that low meiotic recombination rates occur in both parasite populations. These results indicate a role for non-homologous recombination, such as strand-slippage mispairing during mitosis and gene conversion, in creating variation in a malarial antigen under strong diversifying selection.},
	keywords = {Alleles, Animals, Brazil, DNA, Protozoan, Evolution, Molecular, Genetic Variation, Haplotypes, Linkage Disequilibrium, Malaria Vaccines, Merozoite Surface Protein 1, Molecular Sequence Data, Plasmodium falciparum, Polymorphism, Single Nucleotide, Recombination, Genetic, Sequence Analysis, DNA, Tanzania, Thailand, Vietnam},
	issn = {0378-1119},
	author = {Ferreira, Marcelo U and Ribeiro, Weber L and Tonon, Angela P and Kawamoto, Fumihiko and Rich, Stephen M}
}
