A Study Of Certain Aspects Of Human Genetics Including Consanguinity And Genetic Disorders In Human Population Of DG Khan
2009
The consanguineous
marriages are strongly favored in many human populations but their
prevalence and structure vary depending on culture, religion, and
socioeconomic conditions of respective population. These marriages
are reported as the leading cause of enhancing the prevalence of
autosomal recessive genetic disorders.
The challenge of genetic disorders burden in the population calls
for the development of prevention programs. But the strategies for
their implementation require the information about types and
prevalence of genetic disorders and family system in population.
These achievements are possible by thorough understanding of the
determinants of human population genetic structure that is mainly
determined by the marriage pattern. Furthermore, the pattern of
close marriages in population along with other factors leads to
develop the isolated groups having typically confined,
welldocumented, extended and multigenerational pedigrees. The
extended pedigrees with rare disorders are used by geneticists for
their linkage studies. Present study focuses on consanguinity and
genetic disorders in the population of District Dera Ghazi Khan,
Punjab, Pakistan because of its unique geographical location and
population structure.
The district Dera Ghazi Khan is situated in the center of Pakistan,
bounded on the North by Dera Ismail Khan District of N.W.F.P; on the
West by Musa Khel and Barkhan districts of Baluchistan, on the South
by Rajan Pur, and on the East by river Indus that separates it from
all other districts of Punjab province. The population of Dera Ghazi
Khan is mainly a tri-ethnic mixture of Baloch, Natives (Non-Baloch)
and Indian Migrants (Muhajirs). Social and cultural activities vary
in the area but marriages are mostly endogamous within caste or
tribes. The harsh and adverse environmental condition restricts the
movement of people that result in development of extended families
/founder population.
The present study showed 70.52% endogamous marriages in the general
population and 71.62%, 69.62%, and 70.42% in Baloch, Migrant, and
Native populations, respectively. Furthermore high rate of
consanguinity (53.57%) with 0.0301 mean coefficient of inbreeding
was observed in general population. The first-cousin marriages were
found more prevalent. The results were also discussed on the bases
of educational status, occupation, and socioeconomic condition and a
strong link with these factors was observed.
Furthermore, statistically significant effect of consanguinity on
pregnancy loss (miscarriages, abortions, prenatal deaths), and
perinatal deaths (still births, birth of dead child and early
neonatal deaths) were found. In addition, the effect of marriage
types on specific group of genetic disorders like skin disorders
(Albinism, EDs, Alopecia, Aposthia, etc), non-syndromic deafness,
and thalassemia were also studied.
Five families (A, B, C, D, and E) clinically showed the presence of
abnormal nails and skin. In the affected individuals, nychodystrophy
of fingernails and toenails started at the same time but
differentially lead to anonychia on toenails and onycholysis on
fingernails. The skin was abnormal, which bruises and blisters
easily. The affected individuals of these skin families showed
abnormally high sweating, missing finger-prints and palmoplantar
keratoderma. Two families (F, G) exhibited typical features of
congenital alopecia including absence of hair on the scalp, axillae,
pubic, and other parts of the body. In Family F, linkage was
established to hair loss locus on chromosome 8p21. Sequence analysis
of HR gene revealed a single base pair deletion mutation at position
431(431delC) in exon 2, leading to frameshifts and premature
termination codon 68 bp downstream in the same exon. In family G,
genotyping with microsatellite markers failed to detect linkage to
any of the known alopecia / ED locus.
In three families (H, I, J) affected individuals had pre-lingual,
severe to profound hearing loss, with no associated abnormality. The
mode of inheritance of the hearing loss was autosomal recessive.
Analysis of the genotypes revealed the linkage of the family H to
the DFNB35 on chromosome 14, family I, to the locus DFNB44 on
chromosome 7, and family J to the DFNB1 locus on chromosome 13. In
family J, sequence analysis of the coding exon of GJB2 gene led to
the identification of a G-to-A substitution at nucleotide position
71, resulting in a premature stop codon (W24X).
For studying the spectrum of -thalassemia mutations in the
population, 164 -thalassemia chromosomes obtained from 82 different
families were analyzed and nine different mutations [IVS I-5,
FSC8/9, FSC-5 (-CT), IVS-I-1(G-T), CD41/42 (-TTCT), IVS-II-848 (C-A)
and CD 15 (G-A), CD16 (-C) and CD30 (G-C)] in the -globin gene were
detected. Interestingly, frequencies of these mutations vary among
different ethnic groups as well as castes/ tribes.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
0
References
0
Citations
NaN
KQI