Application of Indirect Linkage Analysis for Carrier Detection of Hemophilia A in Kurdistan Region of Iraq: Usefulness of Intron 18 BclI T>A, Intron 19 HindIII C>T, and IVS7 nt27 G>A Markers

Abstract

Hemophilia A (HA) is the most common congenital X-linked coagulopathy caused by mutations in the factor VIII gene. One in 5000 to 10 000 male persons worldwide suffer from HA. It is the archetype of high-cost, low-volume disease. Therefore, identification of carriers is crucial to avoid the birth of affected males. Tracking of the defective X chromosome through indirect linkage analysis represents the most practical method for screening for carriers in developing countries. In this study, 227 individuals from 41 families with HA and 100 normal participants were recruited from the Kurdistan region of Iraq and evaluated for intron 18 Bcl I, intron 19 Hind III, and IVS7 nt 27 markers by polymerase chain reaction restriction fragment length polymorphism and direct sequencing. Among the studied women, 49%, 42%, and 14% were discovered to be heterozygous for Bcl I, Hind III, and IVS7 markers, respectively. Using Bcl I, Hind III, and IVS7 markers, 56%, 46%, and 17% of the families were informative, respectively. The combined informativity of these polymorphic sites reaches 66%. The current study illustrates the effectiveness of the Bcl I and Hind III markers for the diagnosis of HA carriers among the Iraqi Kurdish population.

Accessibility and visibility of genetic testing for haemophilia across Europe: Where do we stand?

“…Widely used prior to the PCR techniques' implementation in the late 1980s, only eight laboratories still offered linkage analysis (Table 3), an indirect method commonly used in developing countries. 26,27 Access to a last update date was considered a guarantee of the test's reliability in a domain where technologies and resources rapidly evolve.…”

“…Of the 17 European GTR‐listed laboratories, only six answered these fields (Tables 3 and 4). Widely used prior to the PCR techniques’ implementation in the late 1980s, only eight laboratories still offered linkage analysis (Table 3), an indirect method commonly used in developing countries 26,27 …”