Muhammad Azhar Iqbal

A splice-site mutation in a retina-specific exon of BBS8 causes nonsyndromic retinitis pigmentosa.

Tissue-specific alternative splicing is an important mechanism for providing spatiotemporal protein diversity. Here we show that an in-frame splice mutation in BBS8, one of the genes involved in pleiotropic Bardet-Biedl syndrome (BBS), is sufficient to cause nonsyndromic retinitis pigmentosa (RP). A genome-wide scan of a consanguineous RP pedigree mapped the trait to a 5.6 Mb region; subsequent systematic sequencing of candidate transcripts identified a homozygous splice-site mutation in a previously unknown BBS8 exon. The allele segregated with the disorder, was absent from controls, was completely invariant across evolution, and was predicted to lead to the elimination of a 10 amino acid sequence from the protein. Subsequent studies showed the exon to be expressed exclusively in the retina and enriched significantly in the photoreceptor layer. Importantly, we found this exon to represent the major BBS8 mRNA species in the mammalian photoreceptor, suggesting that the encoded 10 amino acids play a pivotal role in the function of BBS8 in this organ. Understanding the role of this additional sequence might therefore inform the mechanism of retinal degeneration in patients with syndromic BBS or other related ciliopathies.

GNAT1 associated with autosomal recessive congenital stationary night blindness.

PURPOSE Congenital stationary night blindness is a nonprogressive retinal disorder manifesting as impaired night vision and is generally associated with other ocular symptoms, such as nystagmus, myopia, and strabismus. This study was conducted to further investigate the genetic basis of CSNB in a consanguineous Pakistani family. METHODS A consanguineous family with multiple individuals manifesting cardinal symptoms of congenital stationary night blindness was ascertained. All family members underwent detailed ophthalmic examination, including fundus photographic examination and electroretinography. Blood samples were collected and genomic DNA was extracted. Exclusion and genome-wide linkage analyses were completed and two-point LOD scores were calculated. Bidirectional sequencing of GNAT1 was completed, and quantitative expression of Gnat1 transcript levels were investigated in ocular tissues at different postnatal intervals. RESULTS The results of ophthalmic examinations were suggestive of early-onset stationary night blindness with no extraocular anomalies. The genome-wide scan localized the critical interval to chromosome 3, region p22.1-p14.3, with maximum two-point LOD scores of 3.09 at θ = 0, flanked by markers D3S3522 and D3S1289. Subsequently, a missense mutation in GNAT1, p.D129G, was identified, which segregated within the family, consistent with an autosomal recessive mode of inheritance, and was not present in 192 ethnically matched control chromosomes. Expression analysis suggested that Gnat1 is expressed at approximately postnatal day (P)7 and is predominantly expressed in the retina. CONCLUSIONS These data suggest that a homozygous missense mutation in GNAT1 is associated with autosomal recessive stationary night blindness.

Prevalence of hepatitis B and C in internally displaced persons of war against terrorism in Swat, Pakistan

BACKGROUND Hepatitis B and C are the most common blood-borne liver infections worldwide. According to the recent estimates, 270-300 million people worldwide are infected with hepatitis C virus (HCV) and more than 2 billion people have been infected with the hepatitis B virus (HBV). Transmission of these viruses is carried out by exposure to infectious blood or body fluids containing blood. METHODS Five-hundred and ninety (290 males and 300 females, 5-65 years) internally displaced persons (IDPs) from Swat area of northern Pakistan were screened for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies using immune-chromatography kits. The subjects, positive for virus-related antibody, were further confirmed for viral RNA (for HCV) and DNA (for HBV) in the blood by polymerase chain reaction (PCR) amplification. The virus of PCR-confirmed HCV-individuals was further genotyped and the prevalence of HCV infection was determined with respect to age, sex, history of exposure to blood or surgical operation and different types of liver diseases. RESULTS The HCV infection was found to be the predominant liver infection in the population which was 91% of the positive cases, as against 9% of HBV. Among the HCV-positive subjects (68% females, 32% males) 56% were asymptomatic. No co-incidence of HBV and HCV was found in any subject. Genotype 3a was the dominant strain of HCV followed by 2a > 3b > 1b > 1a, 2b. CONCLUSION The viral hepatitis among the apparently healthy population of a relatively natural and pollution free environment refers to an alarming condition about liver infections, particularly of HCV, in Pakistan.

On Topological Properties of Symmetric Chemical Structures

The utilizations of graph theory in chemistry and in the study of molecule structures are more than someone’s expectations, and, lately, it has increased exponentially. In molecular graphs, atoms are denoted by vertices and bonds by edges. In this paper, we focus on the molecular graph of (2D) silicon-carbon S i 2 C 3 -I and S i 2 C 3 - I I . Moreover, we have computed topological indices, namely general Randic Zagreb types indices, geometric arithmetic index, atom–bond connectivity index, fourth atom–bond connectivity and fifth geometric arithmetic index of S i 2 C 3 -I and S i 2 C 3 - I I .

First Principles Investigation of Fluorine Based Strontium Series of Perovskites

Density functional theory is used to explore structural, elastic, and mechanical properties of SrLiF3, SrNaF3, SrKF3 and SrRbF3 fluoroperovskite compounds by means of an ab-initio Full Potential-Linearized Augmented Plane Wave (FP-LAPW) method. Several lattice parameters are employed to obtain accurate equilibrium volume (Vo). The resultant quantities include ground state energy, elastic constants, shear modulus, bulk modulus, youngs modulus, cauchys pressure, poissons ratio, shear constant, ratio of elastic anisotropy factor, kleinmans parameter, melting temperature, and lames coefficient. The calculated structural parameters via DFT as well as analytical methods are found to be consistent with experimental findings. Chemical bonding is used to investigate corresponding chemical trends which authenticate combination of covalent-ionic behavior. Furthermore electron density plots as well as elastic and mechanical properties are reported for the first time which reveals that fluorine based strontium series of perovskites are mechanically stable and posses weak resistance towards shear deformation as compared to resistance towards unidirectional compression while brittleness and ionic behavior is dominated in them which decreases from SrLiF3 to SrRbF3. Calculated cauchys pressure, poissons ratio and B/G ratio also proves ionic nature in these compounds. The present methodology represents an effective and influential approach to calculate the whole set of elastic and mechanical parameters which would support to understand various physical phenomena and empower device engineers for implementing these materials in numerous applications.

Chemical synthesis of zinc oxide nanorods for enhanced hydrogen gas sensing

Zinc oxide (ZnO) nanorods are prepared using equimolar solution of zinc nitrate ((Zn(NO3)2) and hexamethylenetetramine (C6H12N4) by the hydrothermal technique at 80 °C for 12 h. Epitaxial growth is explored by X-ray diffraction (XRD) patterns, revealing that the ZnO nanorods have a hexagonal (wurtzite) structure. Absorption spectra of ZnO are measured by UV—visible spectrometer. The surface morphology is investigated by field emission scanning electron microscopy (FESEM). The synthesized ZnO nanorods are used for detecting the 150 °C hydrogen gas with a concentration over 1000 ppm. The obtained results show a reversible response. The influence of operating temperature on hydrogen gas detecting characteristic of ZnO nanorods is also investigated.

Y-STR haplotype diversity in Punjabi population of Pakistan

We studied the genetic diversity of 17 Y-chromosomal STR loci (DYS19, DYS385a/b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 and Y-GATA H4) in a sample of 300 genetically unrelated males from Punjabi population of Pakistan. DNA was extracted from blood stains collected on blotting paper (Whatman, Kent, UK) using Phenol chloroform extraction method [1] and quantified using QuantifilerHuman DNA Quantification Kit using ABI 7500 Real-time PCR System. Y-chromosomal STR loci were amplified using AmpFLSTR Yfiler PCR kit with GeneAmp 9700 PCR System (Life Technologies Inc.) according to the manufacturer’s instructions. Amplified products were analyzed by using the ABI PRISM 3100 Genetic Analyzer according to the manufacturer’s recommended protocol. ABI GeneScan 500-LIZ was used as internal size standard along with ABI Hi-Di Formamide. The data were analyzed using ABI GeneMapper ID v3.2. Alleles were designated according to the latest recommendations of the International Society for Forensic Genetics [2]. Haplotype and Allele Frequencies were estimated by simple counting using a spreadsheet program. Discrimination Capacity (DC) of the haplotypes was calculated as DC = H/n, where H is the number of different haplotypes and n is the number of total samples. Estimation of haplotype and gene diversities together with intraand inter-population indices was computed using ARLEQUIN v3.5 [3]. Analysis of molecular variance (AMOVA) was calculated using the AMOVA tool available at YHRD website (www.yhrd.org/Analyse). Total 274 different haplotypes were observed, in which 254 were unique while 20 were observed more than once (Supplementary Table S1). The discrimination capacity was 91.33% while unique haplotypes accounted for 92.7%, showing that these loci are useful for paternity testing and personal identification in the Punjabi population. Locus DYS385 showed the highest diversity (0.9171) while locus DYS391 showed the lowest diversity (0.4137). Supplementary material related to this article can be found, in the online version, at doi:10.1016/j.fsigen.2013.12.004. Punjab (Persian; five waters), is the largest province of Pakistan by population accounting for 56.2% of the country’s population of 180 million (www.census.gov.pk). It is believed that urban civilization existed in the region before the Aryans invasion in around 2500 BC. Occupying a strategically key location, the region has remained part of many empires and civilizations during the course of history. It remained an important hub of Mughal Empire followed by a brief rule by the Sikhs before it fully came under the British Rule and later became part of Pakistan [4]. We compared our data to that of 10 other populations: Afghanistan [Pathan] [5],

Influence of Rare Earth Ho3+ Doping on Structural, Microstructure and Magnetic Properties of ZnO Bulk and Thin Film Systems

We have investigated the doping behavior of rare earth element holmium (Ho3+) in ZnO semiconductor. The structural, microstructure, and magnetic properties of Zn1−xHoxO (x=0.0, 0.04, and 0.05) thin films deposited on Si(100) substrate by thermal evaporation technique were studied. The ceramic targets were prepared by conventional solid state ceramic technique. The pallets used as target were final sintered at 900 °C in the presence of N2 atmosphere. The experimental results of X-ray diffraction (XRD) spectra, surface morphology, and magnetic properties show that the Ho3+ doped ZnO thin films has a strong influence on the materials properties. The higher angle shift in peak position and most preferred (101) orientation were observed in XRD pattern. These spectra confirmed the substitution of Ho3+ in ZnO lattice. The surface morphology and stoichiometry for both bulk and thin films were analyzed by scanning electron microscopy and energy dispersive spectroscopy. It was observed that grain size decreases with the increase of Ho3+. Room temperature ferromagnetism was observed for Zn0.95Ho0.05O films. The ferromagnetism might be attributed to the substitution of Ho ions for Zn2+ in ZnO lattices.

Room Temperature Ferromagnetism in Ga1?xHoxN (x=0.0 and 0.05) Diluted Magnetic Semiconductor Thin Films

Holmium doped GaN diluted magnetic semiconductor thin films have been prepared by thermal evaporation technique and subsequent ammonia annealing. X-ray diffraction measurements reveal all peaks belong to the purely hexagonal wurtzite structure. Surface morphology and composition analysis were carried out by scanning electron microscopy and energy dispersive spectroscopy respectively. The room temperature ferromagnetic properties of Ga1−xHoxN (x=0.0, 0.05) films were analyzed using vibrating sample magnetometer at room temperature. Magnetic measurements showed that the undoped films (i.e. GaN) exhibited diamagnetic behavior, while the Ho-doped (Ga0.95Ho0.05N) film exhibited a ferromagnetic behavior.