scholarly journals Bulk Segregant Approaches to Nutritional Genomics in Plasmodium falciparum

2020 ◽  
Author(s):  
Sudhir Kumar ◽  
Xue Li ◽  
Marina McDew-White ◽  
Ann Reyes ◽  
Abeer Sayeed ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Bovine Serum ◽  
Nutrient Acquisition ◽  
Chromosome 2 ◽  
Aspartate Transaminase ◽  
Differential Growth ◽  
Genome Wide ◽  
Nutritional Genomics ◽  
Frequency Changes ◽  
Strong Candidate

AbstractNutrient acquisition/metabolism pathways provide potent targets for drug design. We conducted crosses between African (NF54) and Asian (NHP4026) malaria parasites, and compared genome-wide allele frequency changes in independent progeny populations grown in human serum or AlbuMAX, a commercial bovine serum formulation. We detected three QTLs linked with differential growth that contained strong candidate genes: aspartate transaminase AST (chromosome 2), cysteine protease ATG4 (chr. 13) and EBA-140 (chr. 14). Alleles inherited from NF54 (chr. 2 and 14) and from NHP4026 (chr. 13) were positively selected in AlbuMAX, while the same alleles were selected against in serum. Selection driving differential growth was strong (s = 0.10 – 0.23 per 48-hour lifecycle) and observed in all biological replicates. These results demonstrate the effectiveness of bulk segregant approaches for revealing nutritional polymorphisms in Plasmodium falciparum. This approach will allow systematic dissection of nutrient acquisition/metabolism pathways that are potential targets for intervention against P. falciparum.

scholarly journals Bulk Segregant Approaches to Nutritional Genomics in Plasmodium falciparum

2021 ◽  
Author(s):  
SUDHIR KUMAR ◽  
Xue Li ◽  
Marina McDew-White ◽  
Ann Reyes ◽  
Abeer Sayeed ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Bovine Serum ◽  
Nutrient Acquisition ◽  
Chromosome 2 ◽  
Aspartate Transaminase ◽  
Differential Growth ◽  
Genome Wide ◽  
Nutritional Genomics ◽  
Frequency Changes ◽  
Strong Candidate

Abstract Nutrient acquisition/metabolism pathways provide potent targets for drug design. We conducted crosses between African (NF54) and Asian (NHP4026) malaria parasites, and compared genome-wide allele frequency changes in independent progeny populations grown in human serum or AlbuMAX, a commercial bovine serum formulation. We detected three QTLs linked with differential growth that contained strong candidate genes: aspartate transaminase AST (chromosome 2), cysteine protease ATG4 (chr. 13) and EBA-140 (chr. 14). Alleles inherited from NF54 (chr. 2 and 14) and from NHP4026 (chr. 13) were positively selected in AlbuMAX, while the same alleles were selected against in serum. Selection driving differential growth was strong (s = 0.10 – 0.23 per 48-hour lifecycle) and observed in all biological replicates. These results demonstrate the effectiveness of bulk segregant approaches for revealing nutritional polymorphisms in Plasmodium falciparum. This approach will allow systematic dissection of nutrient acquisition/metabolism pathways that are potential targets for intervention against P. falciparum.

scholarly journals P170 Differential growth response of Plasmodium falciparum strains in intact bovine serum albumin

2001 ◽  
Vol 52 (Supplement) ◽  
pp. 120
Author(s):  
◽  
Cecilia HUGO ◽  
Yoshihiro URADE ◽  
Toshiro HORII ◽  
Toshihide MITAMURA
Keyword(s):  
Plasmodium Falciparum ◽  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Bovine Serum ◽  
Growth Response ◽  
Differential Growth

scholarly journals Genome-Wide Collation of the Plasmodium falciparum WDR Protein Superfamily Reveals Malarial Parasite-Specific Features

PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0128507 ◽  
Author(s):  
Priyanka Chahar ◽  
Manjeri Kaushik ◽  
Sarvajeet Singh Gill ◽  
Surendra Kumar Gakhar ◽  
Natrajan Gopalan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malarial Parasite ◽  
Protein Superfamily ◽  
Genome Wide

scholarly journals Methylome-wide analysis reveals epigenetic marks associated with resistance to tuberculosis in HIV-infected individuals from East Africa

2020 ◽  
Author(s):  
Catherine Stein ◽  
Penelope Bencheck ◽  
Jacquelaine Bartlett ◽  
Robert P Igo ◽  
Rafal S Sobota ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Sub Saharan Africa ◽  
Chromosome 1 ◽  
Chromosome 2 ◽  
Chromosome 5 ◽  
Epigenetic Marks ◽  
Genome Wide ◽  
A Genome ◽  
Immunodeficiency Virus ◽  
Sub Saharan

Background: Tuberculosis (TB) is the most deadly infectious disease globally and highly prevalent in the developing world, especially sub-Saharan Africa. Even though a third of humans are exposed to Myocbacterium tuberculosis (Mtb), most infected immunocompetent individuals do not develop active TB. In contrast, for individuals infected with both TB and the human immunodeficiency virus (HIV), the risk of active disease is 10% or more per year. Previously, we identified in a genome-wide association study a region on chromosome 5 that was associated with resistance to TB. This region included epigenetic marks that could influence gene regulation so we hypothesized that HIV-infected individuals exposed to Mtb, who remain disease free, carry epigenetic changes that strongly protect them from active TB. To test this hypothesis, we conducted a methylome-wide study in HIV-infected, TB-exposed cohorts from Uganda and Tanzania. Results: In 221 HIV-infected adults from Uganda and Tanzania, we identified 3 regions of interest that included markers that were differentially methylated between TB cases and LTBI controls, that also included methylation QTLs and associated SNPs: chromosome 1 (RNF220, p=4x10-5), chromosome 2 (between COPS8 and COL6A3 genes, p=2.7x10-5), and chromosome 5 (CEP72, p=1.3x10-5). These methylation results colocalized with associated SNPs, methylation QTLs, and methylation x SNP interaction effects. These markers were in regions with regulatory markers for cells involved in TB immunity and/or lung. Conclusion: Epigenetic regulation is a potential biologic factor underlying resistance to TB in immunocompromised individuals that can act in conjunction with genetic variants.

scholarly journals Progressive effects of single-nucleotide polymorphisms on 16 phenotypic traits based on longitudinal data

2020 ◽  
Vol 42 (4) ◽  
pp. 393-403
Author(s):  
Donghe Li ◽  
Hahn Kang ◽  
Sanghun Lee ◽  
Sungho Won
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Longitudinal Data ◽  
Density Lipoprotein ◽  
Phenotypic Traits ◽  
Chromosome 2 ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Longitudinal Changes ◽  
Genome Wide ◽  
A Genome

Abstract Background There are many research studies have estimated the heritability of phenotypic traits, but few have considered longitudinal changes in several phenotypic traits together. Objective To evaluate the progressive effect of single nucleotide polymorphisms (SNPs) on prominent health-related phenotypic traits by determining SNP-based heritability ($$h_{snp}^{2}$$hsnp2) using longitudinal data. Methods Sixteen phenotypic traits associated with major health indices were observed biennially for 6843 individuals with 10-year follow-up in a Korean community-based cohort. Average SNP heritability and longitudinal changes in the total period were estimated using a two-stage model. Average and periodic differences for each subject were considered responses to estimate SNP heritability. Furthermore, a genome-wide association study (GWAS) was performed for significant SNPs. Results Each SNP heritability for the phenotypic mean of all sixteen traits through 6 periods (baseline and five follow-ups) were significant. Gradually, the forced vital capacity in one second (FEV1) reflected the only significant SNP heritability among longitudinal changes at a false discovery rate (FDR)-adjusted 0.05 significance level ($$h_{snp}^{2} = 0.171$$hsnp2=0.171, FDR = 0.0012). On estimating chromosomal heritability, chromosome 2 displayed the highest heritability upon periodic changes in FEV1. SNPs including rs2272402 and rs7209788 displayed a genome-wide significant association with longitudinal changes in FEV1 (P = 1.22 × 10−8 for rs2272402 and P = 3.36 × 10−7 for rs7209788). De novo variants including rs4922117 (near LPL, P = 2.13 × 10−15) of log-transformed high-density lipoprotein (HDL) ratios and rs2335418 (near HMGCR, P = 3.2 $$\times$$× 10−9) of low-density lipoprotein were detected on GWAS. Conclusion Significant genetic effects on longitudinal changes in FEV1 among the middle-aged general population and chromosome 2 account for most of the genetic variance.

138. GENOME-WIDE LINKAGE SCAN FOR FAMILIAL DIZYGOTIC TWINNING

2010 ◽  
Vol 22 (9) ◽  
pp. 56
Author(s):  
J. N. Painter ◽  
G. Willemsen ◽  
D. R. Nyholt ◽  
C. Hoekstra ◽  
D. Duffy ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Complex Trait ◽  
Potential Candidate ◽  
Chromosome 2 ◽  
Family Work ◽  
Linkage Analyses ◽  
Genome Wide ◽  
A Genome ◽  
The Usa ◽  
Genetic And Environmental Factors

The tendency to conceive dizygotic (DZ) twins is a complex trait influenced by genetic and environmental factors. To search for new candidate loci for twinning we have conducted a genome-wide linkage scan in 525 families using microsatellite and single nucleotide polymorphism (SNP) marker panels. Non-parametric linkage analyses including 523 families containing a total of 1115 mothers of DZ twins (MODZT) from Australia and New Zealand (ANZ) and The Netherlands (NL) produced four linkage peaks above the threshold for suggestive linkage, including a highly suggestive peak at the extreme telomeric end of chromosome 6 with an exponential (exp)LOD score of 2.813 (P = 0.0002). Since the DZ twinning rate increases steeply with maternal age independent of genetic effects, we also investigated linkage including only families where at least one MODZT gave birth to her first set of twins before the age of 30. These analyses produced a maximum expLOD score of 2.718 (p = 0.0002), largely due to linkage signal from the ANZ cohort, however, ordered subset analyses indicated this result is most likely a chance finding in the combined dataset. Linkage analyses were also performed for two large DZ twinning families from the USA, one of which produced a peak on chromosome 2 in the region of two potential candidate genes. Sequencing of FSHR and FIGLA, along with INHBB in MODZTs from two large NL families with family-specific linkage peaks directly over this gene, revealed a potentially functional variant in the 5’ untranslated region of FSHR that segregated with the DZ twinning phenotype in the UT family. Work is continuing screening candidate genes. Our data provide further evidence for complex inheritance of familial DZ twinning.

Genome wide gene amplifications and deletions in Plasmodium falciparum

2007 ◽  
Vol 155 (1) ◽  
pp. 33-44 ◽  
Author(s):  
Ulf Ribacke ◽  
Bobo W. Mok ◽  
Valtteri Wirta ◽  
Johan Normark ◽  
Joakim Lundeberg ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Genome Wide
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