Qasim Ayub qa1@sanger.ac.uk

Team 19:Human Evolution http://www.sanger.ac.uk/science/groups/tyler-smith-group

Wellcome Trust Sanger Institute

Wellcome Genome Campus

Hinxton, United Kingdom

Global Globin 2020 Challenge The Human Variome Project

UNESCO, Paris

May 30, 2016

Haemoglobinopathies in Pakistan

A Review

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Outline

Pakistan

Geography

Demography

Population Structure

Haemoglobinoapathies in Pakistan.

Legislation.

Moving forward.

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Pakistan

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Balochistan

Pakistan location map.svg (by NordNordWest)

https://commons.wikimedia.org/w/index.php?curid=16496357

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Khyber Pakhtunkhwa (N.W.F.P.)

Pakistan location map.svg (by NordNordWest)

https://commons.wikimedia.org/w/index.php?curid=16496357

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Punjab

Pakistan location map.svg (by NordNordWest)

https://commons.wikimedia.org/w/index.php?curid=16496357

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Sindh

Pakistan location map.svg (by NordNordWest)

https://commons.wikimedia.org/w/index.php?curid=16496357

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Pakistan

The Burden of Haemoglobinopathies

In Pakistan β-thalassaemia is the most prevalent

among the haemoglobinopathies.

Published estimates indicate that that the carrier rate

is between 5-7% and that there are approximately 8 - 10

million β-thalassaemia carriers in Pakistan.

An estimated 5,000-9,000 new cases of β-thalassaemia

are added each year placing a severe socio-economic

burden.

A rate of 2.4% has been estimated for carriers of alpha-

thalassaemia in the general population in Pakistan.

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Mutation Consequence Phenotype

Allele Frequency

(%) Reference Disease

IVS1-5 Consensus splice site β0 G C 34

Codon 8/9 FRM Frameshift β0 +G 26

619 bp Del Deletion del 10

IVS1-1 Splice junction β0 G T 9

Codon 41/42 FRM Frameshift β0 -TTCT 10

Rare HBB mutations in Pakistan CD 15

CD5

CD 30 (G > C)

CD 30 (G > A)

CAP+1

Fr16

IVSII-1

β- Thalassaemia in Pakistan

IVS1-5

CD 8/9 FRM 619 bp

IVS1-1

CD41/42

Rare

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Northern Pakistan

IVS1-5

CD 8/9 FRM

CD41/42

n = 1,450

IVS1-5

CD 8/9 FRM

CD41/42 n = 537

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Southern Pakistan

IVS1-5

619 bp

n = 270

IVS1-5 n = 651

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α- Thalassemia

Deletions Sindh Punjab Khyber Pakhtunkhwa

(NWFP)

Balochistan

-α4.2

-α3.7

http://prr.hec.gov.pk/thesis/251S.pdf

[Khan SN, 2003; Galanello, 2011; Piel 2014]

Higgs (2013) Cold Spring Harb Perspect Med 2013;3:a011718

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Genetic Screening and Counselling

Pre-marital and pre-natal screening offered in few major

urban centres.

No national coordiantion charitable and non-

governmental organizations.

Premarital advice/screening is inconsistent and patchy.

No genetic counselling service exists and patients

usually personally seek advice from their primary health

care provider or physician.

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Legislation

The bill suggests compulsory pre-marriage screening for

β-thalassaemia

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Pakistan Current Status

http://www.genome.gov/sequencingcosts/

Policy 1

No prevention programme (baseline situation)√

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Summary Centuries of endogamy and high consanguinity

has led to high rates of autosomal recessive

disorders in the Pakistani population, particularly

haemoglobinapathies such as β- thalassaemias.

Molecular characterization reveals that overall five

major mutations account for ~90% of β-

thalassaemia cases. The frequency of these

mutations differs in the major ethic groups.

No overall government policy or disease registry

exists and services are mainly offered by

charitable and non-governmental organizations.

Legislation exists in three of four major

administrative regions of the country, but overall

enforcement is lax.

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Moving Forward

http://www.genome.gov/sequencingcosts/

Establish a national disease registry.

Engage and inform public about disease risk.

Collect molecular epidemiological data from all

ethnicities and geographically regions.

Screen population at risk for 5 common mutations.

Enforce existing regulations regarding pre-marital

screening.

Offer pre-natal diagnosis and genetic counclling

services in all major urban centers.

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Acknowledgements

Human Evolution Team (19)

Hinxton, United Kingdom

Chris Tyler-Smith

Jamil-ur-Rahman Center for Genome Research

University of Karachi Karachi, Pakistan

Ishtiaq Ahmad Khan

Contact:

qa1@sanger.ac.uk