Profiling β-thalassaemia mutations in India at state and regional levels: implications for genetic education, screening and counselling programmes

Sinha, Sujata; Black, Michael; Agarwal, Sarita; Colah, Roshan; Das, Reena; Ryan, Karon; Bellgard, M.; Bittles, Alan H.

doi:10.1007/s11568-010-9132-3

Cited by 76 publications

(72 citation statements)

References 35 publications

(29 reference statements)

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“…Furthermore, at district level in the western Indian states of Maharashtra and Gujurat, β-thalassaemia carrier frequencies ranged from 0% to 9.5% (Colah et al 2010), indicative of the marked demographic and genetic subdivisions within Indian society (Sinha et al 2009). The aim of the present study was to determine comparative national and regional β-thalassaemia mutation profiles for the major countries of South Asia, with the exception of Bangladesh for which only preliminary data have so far been obtained.…”

Section: Introductionmentioning

confidence: 99%

A descriptive profile of β-thalassaemia mutations in India, Pakistan and Sri Lanka

Black

Sinha²,

Agarwal

et al. 2010

J Community Genet

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Thalassaemia is a common and debilitating autosomal recessive disorder affecting many populations in South Asia. To date, efforts to create a regional profile of β-thalassaemia mutations have largely concentrated on the populations of India. The present study updates and expands an earlier profile of β-thalassaemia mutations in India, and incorporates comparable data from Pakistan and Sri Lanka. Despite limited data availability, clear patterns of historical and cultural population movements were observed relating to major β-thalassaemia mutations. The current regional mutation profiles of β-thalassaemia have been influenced by historical migrations into and from the Indian sub-continent, by the development and effects of Hindu, Buddhist, Muslim and Sikh religious traditions, and by the major mid-twentieth century population translocations that followed the Partition of India in 1947. Given the resultant genetic complexity revealed by the populations of India, Pakistan and Sri Lanka, to ensure optimum diagnostic efficiency and the delivery of appropriate care, it is important that screening and counselling programmes for β-thalassaemia mutations recognise the underlying patterns of population sub-division throughout the region.

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Section: Introductionmentioning

confidence: 99%

A descriptive profile of β-thalassaemia mutations in India, Pakistan and Sri Lanka

Black

Sinha²,

Agarwal

et al. 2010

J Community Genet

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“…Mutation HBB.C.92+5 G>C was found to be most common with the frequency of 44.54% for all the samples included in the study (Individual and trio samples also). Frequency of this mutation was found to be 44.8%, 49.8%, 67.9%, 50.7% and 71.4% in north, central, south, east and western Indian population respectively [26]. Frequency of all the mutations found in this study is presented by pie chart in Figure 4.…”

Section: Discussionmentioning

confidence: 49%

“…Out of more than 200 mutations reported for β-thalassemia worldwide [14], mutations included in this study covers 93.5% of Indian populations [26]. Mutation HBB.C.92+5 G>C was found to be most common with the frequency of 44.54% for all the samples included in the study (Individual and trio samples also).…”

Section: Discussionmentioning

confidence: 85%

Whole Gene Sequencing Based Screening Approach to Detect β-Thalassemia Mutations

Chaudhary¹,

Dhawan²,

Sojitra³

et al. 2017

Biol Med (Aligarh)

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About 200 causative mutations are characterized in the β-globin gene. Beta thalassemia diagnosis is very complicated due to the genetic diversity of HBB gene across different geographical regions of the world. In the present study, we have analyzed 138 clinical specimens among them 66 were from 21 unrelated families (trio samples which had DNA from father, mother and chorionic villus sample/amniotic fluid sample) and 72 individual specimens using newly developed sequencing and PCR based assay. We observed 11 different HBB gene mutations in 138 samples, which were also cited by literature as the most prevalent mutations in Indian subcontinent population. The most common mutation observed in our study was HBB.C.92+5 G>C (GC+CC genotype was observed to be 44.93%). Few interesting case studies like co-inheritance of sickle cell anemia and β-thalassemia traits, compound heterozygosity of beta thalassemia major mutation in the case of twin pregnancy were also focused briefly. Commercially available molecular diagnostic kits of HBB gene can detect and identify targeted mutations but will not detect novel and non-targeted mutations of beta thalassemia in parental blood and fetal samples. Hence, a screening technique involving complete sequencing of HBB gene (β-globin gene) is required along with gap PCR approach to provide complete diagnosis of beta thalassemia disease.

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“…In the beginning, elaborate studies in migrant population in UK and USA established the presence of thalassemia mutations in Gujaratis, Punjabis and Sindhis. However, with follow up collaborative studies undertaken in different studies from India, the wide distribution and extensive heterogeneity in different Indian sub-populations became apparent (Sinha et al 2009). With the recognition of several other hematological syndromes both common and rare and the increase in state-of-the-art centers with genetic testing facilities, the mutation database for genetic hematological conditions has seen a great increase in its stock.…”

Section: Molecular Diversity In Genetic Hematological Syndromes In Indiamentioning

confidence: 99%

Abstracts of the Lectures During Haematocon 2013

2013

Indian J Hematol Blood Transfus

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Genetic studies have been included as one of the prerequisites for classification of acute leukemias in the WHO classification of tumors of hematopoietic and lymphoid tissues along with morphology and immunophenotypic features. The cytogenetic and molecular genetic studies are required at the time of diagnosis, not only for recognition of specific genetically defined entities but also for risk stratification and define a baseline against which future studies can be judged to assess clinical progression and response to treatment. Recurring chromosomal translocations that were included in the WHO classification of acute leukemias in 2001 provided clues to better understanding of the process of leukemogenesis and the recognition of various genes located at the breakpoints of these translocations. Many of these chromosomal changes are consistently associated with either myeloid or lymphoid leukemias, and correlate with specific morphologic or immunophenotypic subtypes.Acute lymphoblastic leukemia (ALL) is a heterogenous disease with distinct biological and prognostic groupings. The leukemia is characterized by proliferation of immature B or T cells as a result of various genetic lesions in blood progenitor cells. These genetic lesions are known to have prognostic ramifications. Approximately 75 % of childhood ALL harbor genetic aberrations that are detectable by karyotyping, FISH, or molecular techniques. These include the t(12;21)(p13;q22) and hyperdiploidy which are associated with a good prognosis on one hand and MLL gene rearrangements, e.g. t(4;11) (q21;q23), low hypodiploidy (\40 chromosomes), t(17;19) (q22;p13) (TCF3-HLF),intrachromosomal amplification of chromosome 21 (iAMP21) and t(9;22) (q34;q11) (BCR-ABL) that are associated with poor prognosis. The development of microarray technologies to profile gene expression and structural genetic alterations in a genome-wide and high-resolution fashion have revolutionized our ability to identify genetic abnormalities and have lead to recognition of new entities like BCR/ABL1 like ALL. The development of next-generation sequencing (NGS) technologies have lead to identification of mutations in an array of genes like the PAX5, IKZF1, JAK1/2, CRLF2, IL7R,CREBBP, TP53 and kinase rearrangements and mutations which can be potential molecular targets for the treatment of ALL. Also NGS technology is being used in monitoring the minimal residual disease in ALL.The molecular classification of acute myeloid leukemia (AML) includes recurrent chromosomal structural variations which are well established as both diagnostic and prognostic markers. Patients having PML-RARA, RUNX1-RUNX1T1 and MYH11CBFB fusions are associated with good prognosis and those with 3q abnormalities, monosomy 7, deletion 5q, t(6;9)(p22;q34) are associated with a poor prognosis. However nearly 50 % of AML samples have a normal karyotype and most of these patients lacked structural abnormalities even when assessed with high density comparative genomic hybridization or single nucleotide polymorphism (SNP) arra...

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Profiling β-thalassaemia mutations in India at state and regional levels: implications for genetic education, screening and counselling programmes

Cited by 76 publications

References 35 publications

A descriptive profile of β-thalassaemia mutations in India, Pakistan and Sri Lanka

A descriptive profile of β-thalassaemia mutations in India, Pakistan and Sri Lanka

Whole Gene Sequencing Based Screening Approach to Detect β-Thalassemia Mutations

Abstracts of the Lectures During Haematocon 2013

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