Molecular characterization of β-globin gene mutations in Filipino β-thalassemia patients / Ma. Carmina C. Manuel ; Rita P. Laude, chair, advisory committee.

Date

6-2011

Abstract

The occurrence of β-thalassemia mutations previously reported in Southeast Asians and Filipino migrants was investigated in 55 clinically diagnosed Filipino β-thalassemia patients. The gap-polymerase chain reaction (PCR) involving multiplex primers was employed in detecting the 45-kb Filipino deletion. Other common mutations were detected through PCR amplification of two exons in the human β-globin gene (HBB) followed by direct DNA sequencing. Ten (10) published β-globin gene defects were observed in 35 patients. The β-thalassemia mutations in the other 20 patients remained uncharacterized. Among the observed β-globin gene mutations, Codon 26 (G>A) or Hb E was the most common, accounting for 15.5% (17/110) of the alleles. This was followed by the 45-kb Filipino deletion at 14.5% (16/110) and Codon 67 (-TG) at 9.1% (10/110). These three mutations accounted for 39.1% of the total alleles. The remaining seven mutations were each present at low frequencies (0.9-3.6 %). The uncharacterized alleles comprised 49.1%. Only five of the nine most common mutations found among Southeast Asians were defected in the patient population. The mutations observed in the study participants validated the previously reported spectrum noted in Filipino migrants. In addition, four previously published mutations namely, Codon 17 (A.T), IVS-1.2 (T>C) IVS-1.5 (G>C), and -42 (C>G), were also detected in the study population. The -42 (C.G) allele is a rare mutation even in other populations. This study is the first to report such results. Through the molecular analysis done in this study was limited to only two exons of the β-globin gene, a total of 13 genotypes were fully characterized in the study population suggesting the molecular heterogeneity of β-thalassemia in Filipinos. The detection method used in this study identified β-globin gene mutations in only 63.6% (35/55) of the patients and detected only 50.1% (56/110) β-thalassemia alleles in the study population. To further improve the efficiency of mutation detection, a strategy to detect β-globin gene mutations in Filipino β-thalassemia patients is thus proposed.

Document Type

Dissertation

Degree

Doctor of Philosophy in Genetics

Adviser/Committee Chair

Rita P. Laude

Co-adviser

Catherine Lynn T. Silao

Committee Member

Antonio C. Laurena, Evelyn Mae Tecson-Mendoza, Catherine Lynn T. Silao, Rita P. Laude

Language

English

LC Subject

Molecular genetics, Genetics Institute of Biological Sciences

Location

UPLB Main Library Special Collections Section (USCS)

Call Number

LG 996 2011 G2 M36

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