ABSTRACT
To date, of 13 loci with linkage to non-syndromic autosomal recessive mental retardation (NS-ARMR), only six genes have been established with associated mutations. Here we present our study on NS-ARMR among the Pakistani population, where people are traditionally bound to marry within the family or the wider clan. In an exceptional, far-reaching genetic survey we have collected more than 50 consanguineous families exhibiting clinical symptoms/phenotypes of NS-ARMR. In the first step, nine families (MR2-9 and MR11) with multiple affected individuals were selected for molecular genetic studies. Two families (MR3, MR4) showed linkage to already know NS-ARMR loci. Fifteen affected and 10 unaffected individuals from six (MR2, MR6, MR7, MR8, MR9 and MR11) families were genotyped by using Affymetrix 5.0 or 6.0 single-nucleotide polymorphism (SNP) microarrays. SNP microarray data was visually inspected by dChip and genome-wide homozygosity analysis was performed by HomozygosityMapper. Additional mapping was performed (to exclude false-positive regions of homozygosity called by HomozygosityMapper and dChip) on all available affected and unaffected members in seven NS-ARMR families, using microsatellite markers. In this manner we were able to map three novel loci in seven different families originating from different areas of Pakistan. Two families (MR2, MR5) showed linkage on chromosome 2p25.3-p25.2. Three families (MR7, MR8, and MR9) that have been collected from the same village and belong to the same clan were mapped on chromosome 9q34.3. MR11 maps to a locus on 9p23-p13.3. Analysis of MR6 showed two positive loci, on chromosome 1q23.2-q23.3 and 8q24.21-q24.23. Genotyping in additional family members has so far narrowed, but not excluded the 1q locus. In summary, through this study we have identified three new loci for NS-ARMR, namely MRT14, 15 and 16.
Subject(s)
Consanguinity , Intellectual Disability/genetics , Chromosome Mapping , Female , Genes, Recessive , Genome-Wide Association Study , Humans , Male , Microsatellite Repeats , Pakistan , Pedigree , Polymorphism, Single NucleotideABSTRACT
We evaluated the distribution of ABO and Rhesus (Rh) D blood groups in the population of Poonch district in Azad Jammu and Kashmir. The blood group phenotypes were detected by the classic slide method. The ABO blood group system in the total sample showed the same trend of prevalence as for the general Indian subcontinent (B > or = O > A > AB). The same trend was found among males, but among females the order of prevalence was different (O B > A > AB). However, the allelic frequencies in both sexes were in the order of O > B > A. The Rh positive and negative distribution trend in both sexes was also similar.
Subject(s)
ABO Blood-Group System/genetics , Gene Frequency/genetics , Genetics, Population , Rh-Hr Blood-Group System/genetics , Blood Grouping and Crossmatching/methods , Female , Humans , India , Male , Pakistan , Phenotype , Prevalence , Sex CharacteristicsABSTRACT
We evaluated the distribution of ABO and Rhesus [Rh] D blood groups in the population of Poonch district in Azad Jammu and Kashmir. The blood group phenotypes were detected by the classic slide method. The ABO blood group system in the total sample showed the same trend of prevalence as for the general Indian subcontinent [B >/= O > A > AB]. The same trend was found among males, but among females the order of prevalence was different [O B > A > AB]. However, the allelic frequencies in both sexes were in the order of O > B > A. The Rh positive and negative distribution trend in both sexes was also similar
Subject(s)
Rh-Hr Blood-Group System , Population , Prevalence , Phenotype , ABO Blood-Group SystemABSTRACT
Aposthia (natural circumcision) is the condition of being born without a prepuce. Usually sporadic cases are reported in the medical literature. In this paper for the first time we present the genetic profile of 3 families with aposthia trait and discuss the possible genetics.
Subject(s)
Foreskin/abnormalities , Genes, Recessive/genetics , Genes, Y-Linked/genetics , Hypospadias , Quantitative Trait, Heritable , Circumcision, Male/ethnology , Circumcision, Male/statistics & numerical data , Congenital Abnormalities/epidemiology , Congenital Abnormalities/genetics , Consanguinity , Emigration and Immigration/statistics & numerical data , Genetic Testing , Genetic Variation/genetics , Genetics, Population , Humans , Hypospadias/epidemiology , Hypospadias/genetics , India/ethnology , Islam , Male , Pakistan/epidemiology , Pedigree , Population Surveillance , Residence Characteristics/statistics & numerical data , Surveys and Questionnaires , Urban Health/statistics & numerical dataABSTRACT
Aposthia [natural circumcision] is the condition of being born without a prepuce. Usually sporadic cases are reported in the medical literature. In this paper for the first time we present the genetic profile of 3 families with aposthia trait and discuss the possible genetics
Subject(s)
Genes, Recessive , Health Surveys , ForeskinABSTRACT
We report on a six-generation Pakistani consanguineous family with autosomal recessive transmission of a form of hereditary nail dysplasia. Affected individuals presented with onycholysis of fingernails and anonychia of toenails. Associated abnormalities of ectodermal appendages were not observed in any of the affected individuals. Linkage has been established to chromosome 17q. A maximum multipoint analysis logarithm of the odds ratio score of 4.85 was obtained at marker D17S1301. Due to the consanguineous nature of this kindred, the gene for nail dysplasia is probably contained within a 5.0-cM (3 MB on the sequence-based physical map) region of homozygosity flanked by markers D17S1807 and D17S937.
Subject(s)
Chromosomes, Human, Pair 17/genetics , Nails, Malformed/genetics , Genes, Recessive/genetics , Humans , Nails, Malformed/diagnosis , PedigreeABSTRACT
Nonspecific X-linked mental retardation is a nonprogressive, genetically heterogeneous condition that affects cognitive function in the absence of other distinctive clinical manifestations. We report here linkage data on a large Pakistani family affected by a form of X-linked nonspecific mental retardation. X chromosome genotyping of family members and linkage analysis allowed the identification of a new disease locus, MRX53. The defined critical region spans approximately 15 cM between DXS1210 and DXS1047 in Xq22.2-26. A LOD score value of 3.34 at no recombination was obtained with markers DXS1072 and DXS8081.
