Dataset Information

Investigation of human genetic variants of Hb in Thalassemia patients

ABSTRACT: An investigation of Hb associated human genetic variantions in Pakistani Thalassemia patients

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Homo Sapiens

SUBMITTER: Institute of Biochemistry, Biotechnology and Bioinformatics (IBBB)

PROVIDER: PRJEB50808 | EVA | 2022-02-13

REPOSITORIES: EVA

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			Action	DRS
	HGV_analysis_Thalassemia_merged.vcf.gz	Vcf
	HGV_analysis_Thalassemia_merged.vcf.gz.csi	Vcf
	HGV_analysis_Thalassemia_merged.vcf.gz.tbi	Vcf

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Project description:Background: Recent findings from our group indicate that sex differences in Parkinson's disease (PD) patients with idiopathic conditions or carrying pathogenic mutations significantly influence the blood occurrence of D and L-amino acids, lipids, antioxidants, and energy-related metabolites when compared to healthy controls (HC). In addition to pathogenic mutations, PD patients may also carry rare genetic variants of uncertain significance, whose effects on systemic metabolism have yet to be studied.Methods: We combined untargeted ¹H NMR -based metabolomics to detect broad serum biochemical alterations, with high-performance liquid chromatography (HPLC) analysis of D- and L-amino acids involved in NMDA receptor signaling. The serum metabolome were analyzed in a large cohort of genetically and clinically well-defined PD patients (n = 212) and a balanced group of healthy controls (HC, n = 140). PD patients included idiopathic cases (iPD, n = 121) and those carrying at least one rare variant (rvPD, n = 91) in the following susceptibility genes AIMP2, DNAJC13, DNAJC6, EIF4G1, FBXO7, GIPC1, HMOX2, HSPA8, HTRA2, IMMT, KIF21B, KIF24, LRRK2, MAN2C1, PRKN, RHOT2, SLC25A39, SLC6A3, SNCAIP, SPTBN1, TVP23A, UCHL1, VPS35, ZSCAN21.Results: Multivariate analysis (MVA) of NMR-based measurements identified notable differences between rvPD and HC groups, highlighting significant alterations in 18 metabolic pathways. Male rvPD patients displayed more extensive disruptions in cellular pathways, particularly in several amino acid and glutathione metabolism. In contrast, female patients showed fewer changes, primarily affecting lipid pathways. MVA did not distinguish serum metabolome profiles between iPD and rvPD in either sex, indicating shared biochemical changes in patients with various genetic backgrounds. Notably, HPLC confirmed a significant reduction in L-glutamate among male rvPD patients, a finding not seen in females compared to sex-matched HC. Additionally, L-serine and L-glutamate levels were correlated with MDS-UPDRS III scores in both sexes, with stronger associations observed in male rvPD patients. In line with remarkable alterations in glycine-serine metabolism, association analysis identified Serine Hydroxymethyltransferase 1 (SHMT1), Serine Hydroxymethyltransferase 2 (SHMT2) and Glycine cleavage system H protein, mitochondrial (GCSH) as genetic modifiers for rvPD patients stratified by gender.Conclusion: Our findings highlight the critical influence of sex and rare genetic variants in shaping serum metabolic signatures and their association with motor symptoms in Parkinson's disease.

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Investigation of human genetic variants of Hb in Thalassemia patients

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