Genomics in health and disease

Genomics is the study of all person’s genes including interactions of those genes with each other and person’s environment. Many Factors contribute to human health and disease. Our environment and our biology are two factors that strongly influence our health. For along time, it was believed that disease resulted entirely from our environment or entirely from our biology. Now we are seeing that many human diseases are a result of a complex interaction between our biology and our environment and many other factors. The completion of the Human Genome Project signaled that the genome revolution was here to stay and symbolized its promise that knowing the DNA sequence of our genome and those of hundreds of other organisms would allow us to take on the greatest challenges of human health and alleviate human suffering. The Aim of this review is to discuss the influence of genomics on global health and genetics susceptibility to disease.Key Words: Genomics, genetics, gene regulation, mutation, genetic testing

Sensorineural Hearing Impairment is a Common Feature of Consanguineous Marriage

Introduction: Sensorineural hearing loss (SNHL) accounts for about 60% of all hearing loss. This is sometimes also called “Nerve deafness”. The term “Sensorineural” is used to indicate that there is either a cochlear or an eight nerve lesion. The diagnosis of sensorineural hearing loss is made through audiometry, which shows a significant hearing loss without “The air-bone gap” that is characteristic of conductive hearing disturbances. Among various risk factors described for deafness, consanguinity is an established high risk. Aim of the Work: This work was carried out to study the prevalence of sensorineural hearing loss in offsprings of consanguineous marriage, who attended the Medical Genetics Center, Ain Shams University. Patients and Methods: The study was performed on 950 children with congenital hearing loss. Results: Consanguineous marriage was present in 71.2% of studied cases, 47.3% of these cases, parents were 1st cousin, in 36.7% parents were 2nd cousin, 16% had remote consanguinity. 28.8% of cases were the offspring of non-consanguinous marriage. Also, the results showed that 44.2% of cases had severe degree of sensorineural hearing loss (71-90 dBHL), 24.3% had profound hearing loss (>90 dBHL). Autosomal dominant inheritance (AD) hearing loss was detected in 40% of cases. Autosomal recessive inheritance hearing loss was discovered in 27% of cases, and in 18.7% of study cases the hearing loss was associated with genetic syndromes, where 88.8% of these cases were associated with Down syndrome. Conclusion: The incidence of hereditary hearing impairement is commoner in developing counteries compared to developed counteries, so, prevention is essential to reduce the incidence of genetic hearing loss. Premarital and antenatal screening should be applied whenever possible, at least for those at risk of developing genetic diseases including hearing impairement. Keywords: Consanguinity; hearing disorders; preventive medicine. Egypt. J. Hum. Genet Vol. 9 (1) 2008: pp. 85-9

Evaluation of growth and production of the threatened giant river catfish, Sperata seenghala (Sykes) in polyculture with indigenous major carps

The giant river catfish locally named guizza, Sperata seenghala has significant cultural and economic importance but the fish is now considered as critically endangered due to environmental and manmade interventions in aquatic ecosystem. In order to conserve and rehabilitate this species, an experiment on polyculture of guizza with indigenous major carps was conducted in earthen ponds. Three treatments differing in species ratios and combinations of fish were employed with two replicates each. Treatment-1 (T1) was stocked with catla (Catla catla), rohu (Labeo rohita) and mrigal (Cirrhinus mrigala), treatment-2 (T2) with catla, rohu and guizza (S. seenghala), while treatment-3 (T3) with catla, rohu, mrigal and guizza. Guizza of T2 was introduced instead of mrigal in T1 and 50% of mrigal was replaced with guizza in T3. The stocking density of fish fingerlings in all the treatments was 7500 individual/ha. Fishes in the experimental ponds were fed with supplementary diet comprising of rice bran (50%), mustard oil cake (30%), fish meal (19%) and vitamin-mineral premix (1%). Physicochemical parameters and plankton populations were within the appropriate levels for aquaculture. Mean growth and survival of catla and rohu were significantly higher in T2 than in T3 and T1. Guizza in T2 showed higher performances than in T3, while those for mrigal were higher in T3 than T1 (p < 0.05). The total gross and net productions of fishes were higher in T3 than in T2 and T1 (p < 0.05). This trial is a successful attempt to culture the threatened guizza with major carps in earthen ponds, the findings of which would immensely be helpful towards the development of aquaculture and conservation of this important fish in captive condition.Key words: Riverine catfish, Sperata seenghala, polyculture, earthen ponds

Co-solute assistance in refolding of recombinant proteins

Prokaryotic expression system is the most widely used host for the production of recombinant proteins but inclusion body formation is a major bottleneck in the production of recombinant proteins in prokaryotic cells, especially in Escherichia coli. In vitro refolding of inclusion body into the the proteins with native conformations is a solution for this problem but there is a need for optimization of condition for each protein specifically. Several approaches have been described for in vitro refolding; most of them involve the use of additives for assisting correct refolding. Co-solutes play a major role in refolding process and can be classified according to their function as, aggregation suppressors and folding enhancers. This study presents a review of additives that are used in refolding process of insoluble recombinant proteins in small scale and industrial process.Key words: Refolding, protein aggregation, low-molecular-weight additives, arginine

Role of three side support ankle–foot orthosis in improving the balance in children with spastic diplegic cerebral palsy

Cerebral palsy (CP) is a heterogeneous group of permanent, non-progressive motor disorders of movement and posture. Ankle–foot orthoses (AFOs) are frequently prescribed to correct skeletal misalignments in spastic CP. The present study aims to evaluate the effect of the three side support ankle–foot orthosis on standing balance of the spastic diplegic CP children. Thirty spastic diplegic CP children participated in this study from both sexes. They were divided randomly intotwo age and sex matched groups: (Group I: study group and Group II: control group). The degree of spasticity was evaluated by passive movement for both limbs, while the child was completely relaxed. The Biodex stability system, was used for the assessment of the dynamic postural control of all diplegic children. Also the system measures the subject’s ability to control the platform’s angle of tilt. The patient’s performance is noted as stability index which represents the variance of the platform displacement in degrees. Every patient in the study group was exercised on three side support ankle–foot orthosis for 30 min, three times weekly, for 6 months, also they received the same therapeutic exercise program which was given to the control group. The results revealed no significant difference as regards the pre-treatment mean values of all stability indices in both the control and the study groups (P< 0.05). However comparison between post-treatment mean values of allstability indices in both groups showed significant improvement in favor of the study group (p<0.05). In conclusion: Uses of the three side support ankle–foot orthosis in addition to physical exercise program is highly useful in rehabilitation of spastic diplegic cerebral palsy children as theyenabled them to gain more balance control and postural reactions

Risk factors for autism: An Egyptian study

This study has been conducted to determine the possible risk factors of autism. This case control study was conducted at pediatric hospital, Ain Shams University on, 100 autistic patients who were subjected to the followings tools: Confirmation of diagnosis using DSM-IV-TR criteria,IQ assessment using Stanford–Binrent intelligence scale, and assessment of severity of autistic symptoms using childhood autism rating scale (CARS). Full clinical examination, neurological examination, EEG and audiological assessment were also done. Forty-six percent of our patientswith autistic symptoms presented at the age of one and half years and 32% at the age of 2 years. Fifty-five percent of our patients had mild to severe retardation (IQ = 20–70), 36% below average mentality (IQ = 71–89) and 9% with normal mentality (IQ = 90–109). High maternal age (mother, P35 years) at birth was found in 23% of autistic children in comparison to 9.5% of controls. Also advanced paternal age (father, P35 years) at birth was found in 91% of cases in comparison to 83.5% of control group and the difference was statistically significant. Positive family history was found to be statistically significantly associated with the risk of autism (16% of cases versus 1% of control). All studied developmental milestones were delayed among autistic children than control group (p= 0.000). As regards natal factors, a history of low birth weight, delivery by ceserian section were significantly higher among cases than controls. Also postnatal factors as history of hypoxia, resuscitation and history of jaundice were considered significantly risk factors for autism (p=0.000)

Fetal chromosome abnormalities and congenital malformations: an Egyptian study

Objective: Our objective were to determine and evaluate the role of genetic counseling and amniocentesis in early detection of chromosomal abnormalities or congenital malformations among women at risk. Patients and Methods: The study was performed on 784 pregnant women. Results: The cause for seeking genetic counseling in 22.8% of the study cases was positive family history of CNS malformations, and in 17.9% was chromosomal abnormalities in previous child. Also, the results showed that the indications for amniocentesis in 60.8% were history of having previous child with Down syndrome, and in 15.3% were advanced maternal age. The results of chromosomal analysis of amniotic fluid samples; 21 cases (19.3%) had chromosomal abnormalities, where trisomy 21 (Down syndrome) was detected in 10 cases (9.2%), unbalanced translocation Down syndrome was detected in 9 cases (8.3%) and one had 46 XX, del (13-q), one had 45, XX, t (13;14) and 2.8% was 46, XX, +21, der (14;21) (q10;q10). The risk of complications of amniocentesis was associated with performing amniocentesis early in pregnancy, and with increased number of attempts. The results also showed that Multiple congenital anomalies (MCA) represented among 42.2%, congenital malformation of CNS represents 26.6%, congenital malformation of the skeletal system 20%, congenital polycystic kidney 8.8% and pyloric stenosis in 2.2%. Among the 21 women with abnormal karyotype of amniotic fluid, the decision to terminate the pregnancy was made in 3 (14.3%). Among the 45 cases with abnormal findings suggesting fetal congenital malformation, 16 (35.6%) chose termination of their pregnancy. In conclusion: Public awareness of the risks and difficulties facing a child with chromosomal anomalies or congenital malformations and the effect on their future health and living is of great importance for acceptance of prenatal screening. Prenatal diagnosis may affect the reproductive decision after genetic counseling. It is essential that genetic counseling is noncoercive and nonjudjemental. The couples decision (Even if it is different from the counselor's views) should be respected. Keywords: Genetic counselling, antenatal screening, amniocentesis. Egypt. J. Hum. Genet Vol. 8 (2) 2007: pp. 131-14

Ocular features in Egyptian genetically disabled children

Ocular changes in genetically disabled children are great and of special importance. The aim of the present study was to delineate the nature and frequency of ocular defects in genetically disabled children. A cross sectional study was carried out. It included 95 genetically disabled children who were chosen from the medical genetics and ophthalmic departments, Ain-Shams University Hospitals, and examined for any associated ocular abnormalities. Studied patients were divided into six groups (Group I: Chromosomal disorders (Down syndrome), Group II: Genetic syndromes, Group III: Cranial anomalies, Group IV: Inborn errors of metabolism (IEM), Group V: Cerebral palsy, Group VI: Mental retardation). Anomalies of the eyelids were detected in 63.1% of our patients. They were significantly increased in group I [Chromosomal disorders (Down syndrome)], compared to other groups. Errors of refraction were detected in all Down syndrome patients.On the other hand some ocular findings were present in our Down syndrome patients and not reported in the literature before; these include, lacrimal fistula, lagophthalmos, heterochromia, macrocornea and ectropion in 3.3% of patients, tortous retinal vessels, entropion, and prominent upper punctum in 6.6%, ptosis in 10%, microcornea, absent foveal reflex, and blepharophimosis in 13.3% of our cases. Lacrimal apparatus abnormalities were detected in 11.5% of our patients, the highest frequency was detected among the chromosomal disorder group 27%. Conjunctival and scleral abnormalities were also detected in 10.5% of our patients, where the group of chromosomal disorders had the highest frequency (20%). Cornea and anterior chamber abnormalities were detected in 30.5%, these abnormalities had the same frequency (33%) in the groups of chromosomal disorders, genetic syndromes and inborn errors of metabolism. Iris and pupil abnormalities were detected in 15.7% of our patients. Lens abnormalities were detected in 10.5% of our patients, where the group of inborn errors of metabolism had the highest frequency (44%). Ocular muscles and mobility abnormalities were diagnosed in 47.3% of our patients. Fundus examination revealed abnormalities in 34.7% of patients,where the group  of cerebral palsy had the highest frequency (50%).Our results emphasize that, the earlier and better the visual sense function, the greater the chance the child will achieve his potential.The ophthalmologist, paediatricians, geneticists must work hand in hand for detection of ocular disorders in genetically disabled children to initiate diagnostic and therapeutic measures to control the disease. Keywords: Disability; Genetics; Ocular changes; Handicap; Chromosomal  abnormalitie

Environmental bacteriophages active on biofilms and planktonic forms of toxigenic Vibrio cholerae: Potential relevance in cholera epidemiology.

METHODS: Phages isolated from environmental waters in Bangladesh were tested for their host specificity towards V. cholerae O1 and O139, and the ability to disperse V. cholerae biofilms formed in the laboratory. Representative phages were further characterized by electron microscopy and whole genome sequencing. Selected phages were then introduced in various combinations to biofilms of toxigenic V. cholerae added to samples of river water, and the dispersion of biofilms as well as the growth kinetics of V. cholerae and the phages were monitored. RESULTS: A phage cocktail composed of three different phages isolated from surface waters in Bangladesh and designated as JSF7, JSF4, and JSF3 could significantly influence the distribution and concentration of the active planktonic form and biofilm associated form of toxigenic V. cholerae in water. While JSF7 showed a biofilm degrading activity and dispersed cells from both V. cholerae O1 and O139 derived biofilms thus increasing the concentration of planktonic V. cholerae in water, JSF4 and JSF3 showed strong bactericidal activity against V. cholerae O1 and O139 respectively. A mixture of all three phages could effectively reduce both biofilm-associated and planktonic V. cholerae in river water microcosms. SIGNIFICANCE: Besides potential applicability in phage-mediated control of cholera, our results have relevance in appreciating possible intricate role of diverse environmental phages in the epidemiology of the disease, since both biofilms and phages influence the prevalence and infectivity of V. cholerae in a variety of ways