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Table 6 Genes identified by GWAS associated with fatty acid and cholesterol metabolism

From: Global-scale GWAS associates a subset of SNPs with animal-adapted variants in M. tuberculosis complex

SNP

p-value

score

G1P1

G0P0

G1P0

G0P1

Locus

Protein

Change

Description

Notes

181,672

0

0.951

4100

2100

161

1

Rv0153c

PtbB

Asp105Gly

Phosphotyrosine protein phosphatase PTPB (protein-tyrosine-phosphatase) (PTPase)

Required for growth on cholesterol (Griffin 2011)

294,198

0

0.997

4100

2250

9

8

Rv0244c

FadE5

Glu479Ala

Probable acyl-CoA dehydrogenase FadE5

Required for growth on cholesterol (Griffin 2011)

1,684,979

0

0.948

4100

2080

172

1

Rv1493

MutB

Synonymous

Probable methylmalonyl-CoA mutase large subunit MutB (MCM)

Downstream in cholesterol to propionyl-CoA metabolic pathways (Wilburn 2018)

1,754,572

0

0.951

4100

2100

161

1

Rv1550

FadD11

Leu286Ser

Probable fatty-acid-CoA ligase FadD11 (fatty-acid-CoA synthetase) (fatty-acid-CoA synthase)

 

2,997,325

0

0.951

4100

2100

161

1

Rv2681

 

Ala196Val

Conserved hypothetical alanine rich protein

Required for growth on cholesterol (Griffin 2011)

3,223,303

0

0.997

4100

2250

9

8

Rv2914c

PknI

Synonymous

Probable transmembrane serine/threonine-protein kinase I PknI (protein kinase I) (STPK I) (phosphorylase B kinase kinase) (hydroxyalkyl-protein kinase)

Required for growth on cholesterol (Griffin 2011), mutant shows increased growth in THP-1 cells, SCID mice show faster mortality with mutant (Gopalaswamy 2009)

3,912,636

0

0.951

4100

2100

162

1

Rv3494c

Mce4F

Asp245Gly

Mce-family protein Mce4F

Required for growth on cholesterol (Griffin 2011)

3,924,350

0

0.951

4100

2100

161

1

Rv3505

FadE27

Ala218Val

Probable acyl-CoA dehydrogenase FadE27

 

3,987,645

0

0.997

4100

2250

9

8

Rv3548c

 

Met218Val

Probable short-chain type dehydrogenase/reductase

Required for growth on cholesterol (Griffin 2011)

4,004,604

0

0.997

4100

2250

9

8

Rv3563

FadE32

Gln105Arg

Probable acyl-CoA dehydrogenase FadE32

Required for growth on cholesterol (Griffin 2011), essential in murine spleen (Sassetti and Rubin, 2003)

3,254,695

0

0.951

4100

2100

161

1

Rv2932

PpsB

Synonymous

Phenolpthiocerol synthesis type-I polyketide synthase PpsB

In vitro essential in CDC1551 (Lamichhane 2003), not in H37Rv (Griffin 2011; DeJesus 2017; Minato 2019)

3,262,628

0

0.951

4100

2100

161

1

Rv2934

PpsD

Met127Ile

Phenolpthiocerol synthesis type-I polyketide synthase PpsD

 

3,267,715

0

0.951

4100

2100

161

1

Rv2934

PpsD

Glu1823Ala

Phenolpthiocerol synthesis type-I polyketide synthase PpsD

 

3,320,554

0

0.951

4100

2100

161

1

Rv2947c

Pks15

Synonymous

Probable polyketide synthase Pks15, involved in the biosynthesis of phenolphthiocerol glycolipids

 
  1. A subset of genes in the pathways of lipid and cholesterol intake, metabolism, and utilization were identified with SNPs by GWAS, with a split roughly between one genotype in MTB ± MOR and a divergent genotype in MBO ± MCP. Columns 2–5 indicate presence of genotype G (SNP = 1, WT = 0) and phenotype P (MBO classification = 1, non-MBO classification = 0). The misclassification of 9 MBO isolates as MTB, and 1 MTB isolate as MBO (Tables 4, 5) are evident in the G1P0 and G0P1 columns for many variants