Search results for: genetic mutation

Authors: Damaris Estrella Castillo, Zacil ha Vilchis Zapata, Leydi Peraza Gómez

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Hearing loss is an etiologically heterogeneous condition, where almost 60% is genetic in origin, 20% is due to environmental factors, and 20% have unknown causes. However, it is now known that the gene, GJB2, which encodes the connexin 26 protein, accounts for a large percentage of non-syndromic genetic hearing loss, and variants in this gene have been identified to be a common cause of hereditary hearing loss in many populations. The literature reports that the etiology in deafness helps improve family functioning but low-income countries this is difficult. Therefore, it is difficult to contribute the right of families to know about the genetic risk in future pregnancies as well as determining the certainty of being a carrier or affected. In order to assess the impact of genetic counseling and the functionality, 100 families with at least one child with profound hearing loss, were evaluated by specialists in audiology, clinical genetics and psychology. Targeted mutation analysis for one of the two known large deletions of upstream of GJB2/GJB6 gene (35delG; and including GJB2 regulatory sequences and GJB6) were performed in patients with diagnosis of non-syndromic hearing loss. Genetic counseling was given to all parents and primary caregivers, and APGAR family test was applied before and after the counseling. We analyzed a total of 300 members (children, parents) to determine the presence of the GJB2 gene mutation. Twelve patients (carriers and affected) were positive for the mutation, from 5 different families. The subsequent family APGAR testing and genetic counseling, showed that 14% perceived their families as functional, 62 % and 24 % moderately functional dysfunctional. This shows the importance of genetic counseling in the perception of family function that can directly impact the quality of life of these families.

Keywords: family dynamics, deafness, APGAR, counseling

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Authors: Seraj Makkawi, Abdulaziz A. Alqarni, Himyan Alghaythee, Suzan Y. Alharbi, Anmar Fatani, Reem Adas, Ahmad R. Abuzinadah

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Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disease that involves both the upper and lower motor neurons. Familial ALS, including superoxide dismutase 1 (SOD1) mutation, accounts for 5-10% of all cases of ALS. Typically, the symptoms of ALS are purely motor, though coexistent sensory symptoms have been reported in rare cases. In this report, we describe the case of a 47- year-old man who presented with progressive bilateral lower limb weakness and numbness for the last four years. A nerve conduction study (NCS) showed evidence of coexistent axonal sensorimotor polyneuropathy in addition to the typical findings of ALS in needle electromyography. Genetic testing confirmed the diagnosis of familial ALS secondary to the SOD1 genetic mutation. This report highlights that the presence of sensory symptoms should not exclude the possibility of ALS in an appropriate clinical setting.

Keywords: Saudi Arabia, polyneuropathy, SOD1 gene mutation, familial amyotrophic lateral sclerosis, amyotrophic lateral sclerosis

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Authors: Mohammed N. Al Kindi, Mazin Al Khabouri, Khalsa Al Lamki, Tommasso Pappuci, Giovani Romeo, Nadia Al Wardy

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Hereditary hearing loss is a heterogeneous group of complex disorders with an overall incidence of one in every five hundred newborns presented as syndromic and non-syndromic forms. Cadherin-related 23 (CDH23) is one of the listed deafness causative genes. CDH23 is found to be expressed in the stereocilia of hair cells and the retina photoreceptor cells. Defective CDH23 has been associated mostly with prelingual severe-to-profound sensorineural hearing loss (SNHL) in either syndromic (USH1D) or non-syndromic SNHL (DFNB12). An Omani family diagnosed clinically with severe-profound sensorineural hearing loss was genetically analysed by whole exome sequencing technique. A novel homozygous missense variant, c.A7451C (p.D2484A), in exon 53 of CDH23 was detected. One hundred and thirty control samples were analysed where all were negative for the detected variant. The variant was analysed in silico for pathogenicity verification using several mutation prediction software. The variant proved to be a pathogenic mutation and is reported for the first time in Oman and worldwide. It is concluded that in silico mutation prediction analysis might be used as a useful molecular diagnostics tool benefiting both genetic counseling and mutation verification. The aspartic acid 2484 alanine missense substitution might be the main disease-causing mutation that damages CDH23 function and could be used as a genetic hearing loss marker for this particular Omani family.

Keywords: Cdh23, d2484a, in silico, Oman

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Authors: Khaled Salah

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In this paper, we present MCERTL (mutation-based correction engine for RTL designs) as an automatic error correction technique based on mutation analysis. A mutation-based correction methodology is proposed to automatically fix the erroneous RTL designs. The proposed strategy combines the processes of mutation and assertion-based localization. The erroneous statements are mutated to produce possible fixes for the failed RTL code. A concurrent mutation engine is proposed to mitigate the computational cost of running sequential mutants operators. The proposed methodology is evaluated against some benchmarks. The experimental results demonstrate that our proposed method enables us to automatically locate and correct multiple bugs at reasonable time.

Keywords: bug localization, error correction, mutation, mutants

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Authors: Mohammad Jalali Varnamkhasti

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The genetic algorithms have been very successful in handling difficult optimization problems. The fundamental problem in genetic algorithms is premature convergence. This paper, present a new fuzzy genetic algorithm based on chaotic values instead of the random values in genetic algorithm processes. In this algorithm, for initial population is used chaotic sequences and then a new sexual selection proposed for selection mechanism. In this technique, the population is divided such that the male and female would be selected in an alternate way. The layout of the male and female chromosomes in each generation is different. A female chromosome is selected by tournament selection size from the female group. Then, the male chromosome is selected, in order of preference based on the maximum Hamming distance between the male chromosome and the female chromosome or The highest fitness value of male chromosome (if more than one male chromosome is having the maximum Hamming distance existed), or Random selection. The selections of crossover and mutation operators are achieved by running the fuzzy logic controllers, the crossover and mutation probabilities are varied on the basis of the phenotype and genotype characteristics of the chromosome population. Computational experiments are conducted on the proposed techniques and the results are compared with some other operators, heuristic and local search algorithms commonly used for solving p-median problems published in the literature.

Keywords: genetic algorithm, fuzzy system, chaos, sexual selection

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Authors: Iyad Alazzam, Kenneth Magel, Izzat Alsmadi

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The different activities and approaches in software testing try to find the most possible number of errors or failures with the least amount of possible effort. Mutation is a testing approach that is used to discover possible errors in tested applications. This is accomplished through changing one aspect of the software from its original and writes test cases to detect such change or mutation. In this paper, we present a mutation approach for testing software components integration aspects. Several mutation operations related to components integration are described and evaluated. A test case study of several open source code projects is collected. Proposed mutation operators are applied and evaluated. Results showed some insights and information that can help testing activities in detecting errors and improving coverage.

Keywords: software testing, integration testing, mutation, coverage, software design

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Authors: B. Falah, N. E. Abakouy

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Due to its high computational cost, mutation testing has been neglected by researchers. Recently, many cost and mutants’ reduction techniques have been developed, improved, and experimented, but few of them has relied the possibility of reducing the cost of mutation testing on the program type of the application under test. This paper is a comparative study between four operators’ selection techniques (mutants sampling, class level operators, method level operators, and all operators’ selection) based on the program code type of each application under test. It aims at finding an alternative approach to reveal the effect of code type on mutation testing score. The result of our experiment shows that the program code type can affect the mutation score and that the programs using polymorphism are best suited to be tested with mutation testing.

Keywords: equivalent mutant, killed mutant, mutation score, mutation testing, program code type, software testing

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Authors: Arab M., Ait Abdallah M., Zeraoulia N., Boumaza H., Aoutia M., Griene L., Ait Abdelkader B.,

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breast and ovarian cancer are respectively the first and fourth leading causes of cancer among women in Algeria. A family story of cancer in the most important risk factor, and in most cases of families with breast and /or ovarian cancer, the pattern of cancer family can be attributed to mutation in BRCA1/2genes. objectibes: the aim of our study in to investigate the spectrum of BRCA1/2 germiline mutation in familial breast and /or ovarian cancer and to determine the prevalence and the nature of BRCA1/2mutation in Algeria methods: we deremined the prevalence of BRCA1/2 mutation within a cohort of 161 probands selected according the eisinger score double stranded sanger sequencing of all coding exons of BRCA1/2including flanking intronic region were performed results: we identified a total of 23 distinct deleterious mutations (class5) 12 differents mutations in BRCA1(52%) and 11 in BRCA2(48%). 78% (18/23) were protein truncating and 22%(5/23) missens mutations.3 novel deleterious mutations have been identified, which have not been described in public mutation database. one new mutation were found in two unrelated patients. the overall mutation detection rate in our study is 28,5%(46/161).more over, an UVS c7783 located in BRCA2 is found in two unrelated probands and segregate in the 02 families/ conclusion: our results sugget of large spectrum of BRCA1/2 mutation in Algerian breast/ovarian cancer family. The nature and prevalence of BRCA1/2mutation in algerian families are ongoing in a larger study, 80 probands are to day under investigation. This study which may therefore identify the genetic particularity of Algerian breast /ovarian cancer.

Keywords: BRCA1/2 mutations, hereditary breast cancer, algerian women, prvalence

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Authors: Huong M. T. Nguyen, Hoa A. P. Nguyen, Chi V. Phan, Mai P. T. Nguyen, Ngoc D. Ngo, Van T. Ta, Hai T. Le

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Wilson’s disease is an autosomal recessive disorder of copper metabolism, which is caused by mutation in copper- transporting P-type ATPase (ATP7B). The mechanism of this disease is a failure of hepatic excretion of copper to the bile, and it leads to copper deposits in the liver and other organs. Most clinical symptoms of Wilson’s disease can present as liver disease and/or neurologic disease. Objective: The goal of the study is prenatal diagnosis for pregnant women at high risk of Wilson’s disease in Northern Vietnam. Material and method: Three probands with clinically diagnosed liver disease were detected in the mutations of 21 exons and exon-intron boundaries of the ATP7B gene by direct Sanger-sequencing. Prenatal diagnoses were performed by amniotic fluid sampling from pregnant women in the 16th-18th weeks of pregnancy after the genotypes of parents with the probands were identified. Result: A total of three different mutations of the probands, including of S105*, P1052L, P1273G, were detected. Among three fetuses which underwent prenatal genetic testing, one fetus was homozygote; two fetuses were carriers. Conclusion: Genetic testing provided a useful method for prenatal diagnosis, and is a basis for genetic counseling.

Keywords: ATP7B gene, genetic testing, prenatal diagnosis, pedigree, Wilson disease

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Authors: Wafa’ Alma'Aitah, Khaled Almakadmeh

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this study presents an information retrieval system of using genetic algorithm to increase information retrieval efficiency. Using vector space model, information retrieval is based on the similarity measurement between query and documents. Documents with high similarity to query are judge more relevant to the query and should be retrieved first. Using genetic algorithms, each query is represented by a chromosome; these chromosomes are fed into genetic operator process: selection, crossover, and mutation until an optimized query chromosome is obtained for document retrieval. Results show that information retrieval with adaptive crossover probability and single point type crossover and roulette wheel as selection type give the highest recall. The proposed approach is verified using (242) proceedings abstracts collected from the Saudi Arabian national conference.

Keywords: genetic algorithm, information retrieval, optimal queries, crossover

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Authors: D. Estrella, A. Silva, R. Zapata, H. Rubio

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A total of 100 primary caregivers (mothers, fathers, grandparents) with at least one child or grandchild with a diagnosis of congenital bilateral profound deafness were assessed in order to evaluate the functionality of families with a deaf member, who was evaluated by specialists in audiology, molecular biology, genetics and psychology. After confirmation of the clinical diagnosis, DNA from the patients and parents were analyzed in search of the 35delG deletion of the GJB2 gene to determine who possessed the mutation. All primary caregivers were provided psychological support, regardless of whether or not they had the mutation, and prior and subsequent, the family APGAR test was applied. All parents, grandparents were informed of the results of the genetic analysis during the psychological intervention. The family APGAR, after psychological and genetic counseling, showed that 14% perceived their families as functional, 62% moderately functional and 24% dysfunctional. This shows the importance of psychological support in family functionality that has a direct impact on the quality of life of these families.

Keywords: deafness, psychological support, family, adaptation to disability

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Authors: Michael Stewart

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Mutation testing is a type of software testing proposed in the 1970s where program statements are deliberately changed to introduce simple errors so that test cases can be validated to determine if they can detect the errors. Test cases are executed against the mutant code to determine if one fails, detects the error and ensures the program is correct. One major issue with this type of testing was it became intensive computationally to generate and test all possible mutations for complex programs. This paper used reinforcement learning and parallel processing within the context of mutation testing for the selection of mutation operators and test cases that reduced the computational cost of testing and improved test suite effectiveness. Experiments were conducted using sample programs to determine how well the reinforcement learning-based algorithm performed with one live mutation, multiple live mutations and no live mutations. The experiments, measured by mutation score, were used to update the algorithm and improved accuracy for predictions. The performance was then evaluated on multiple processor computers. With reinforcement learning, the mutation operators utilized were reduced by 50 – 100%.

Keywords: automated-testing, machine learning, mutation testing, parallel processing, reinforcement learning, software engineering, software testing

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Authors: Huong M. T. Nguyen, Hoa A. P. Nguyen, Mai P. T. Nguyen, Ngoc D. Ngo, Van T. Ta, Hai T. Le, Chi V. Phan

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Wilson’s disease (WD) is an autosomal recessive disorder of the copper metabolism, which is caused by a mutation in the copper-transporting P-type ATPase (ATP7B). The mechanism of this disease is the failure of hepatic excretion of copper to bile, and leads to copper deposits in the liver and other organs. The ATP7B gene is located on the long arm of chromosome 13 (13q14.3). This study aimed to investigate the gene mutation in the Vietnamese patients with WD, and make a presymptomatic diagnosis for their familial members. Forty-three WD patients and their 65 siblings were identified as having ATP7B gene mutations. Genomic DNA was extracted from peripheral blood samples; 21 exons and exon-intron boundaries of the ATP7B gene were analyzed by direct sequencing. We recognized four mutations ([R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G) in the sum of 20 detectable mutations, accounting for 87.2% of the total. Mutation S105* was determined to have a high rate (32.6%) in this study. The hotspot regions of ATP7B were found at exons 2, 16, and 8, and intron 14, in 39.6 %, 11.6 %, 9.3%, and 7 % of patients, respectively. Among nine homozygote/compound heterozygote siblings of the patients with WD, three individuals were determined as asymptomatic by screening mutations of the probands. They would begin treatment after diagnosis. In conclusion, 20 different mutations were detected in 43 WD patients. Of this number, four novel mutations were explored, including [R723=; H724Tfs*34], V1042Cfs*79, D1027H, and IVS6+3A>G. The mutation S105* is the most prevalent and has been considered as a biomarker that can be used in a rapid detection assay for diagnosis of WD patients. Exons 2, 8, and 16, and intron 14 should be screened initially for WD patients in Vietnam. Based on risk profile for WD, genetic testing for presymptomatic patients is also useful in diagnosis and treatment.

Keywords: ATP7B gene, mutation detection, presymptomatic diagnosis, Vietnamese Wilson’s disease

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Authors: Aminah Muchdar

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To increase the genetic diversity of soybean in order to adapt to agroecology in Indonesia conducted ways including introduction, cross, mutation and genetic transformation. The purpose of this research is to obtain early maturity soybean mutant lines, large seed tolerant to drought with high yield potential. This study consisted of two stages: the first is sensitivity of gamma rays carried out in the Laboratory BATAN. The genetic variety used is Anjasmoro. The method seeds irradiated with gamma rays at a rate of activity with the old ci 1046.16976 irradiation 0-71 minutes. Irradiation doses of 0, 100, 200, 300, 400, 500, 600, 700, 800, 900 and 1000gy. The results indicated all seeds irradiated with doses of 0 - 1000gy, just a dose of 200 and 300gy are able to show the percentage of germination, plant height, number of leaves, number of normal sprouts and green leaves of the best and can be continued for a second trial in order to assemble and to get mutants which is expected. The result of second stage of soybean M2 Population irradiated with diversity Gamma Irradiation performed that in the form of soybean planting, the seed planted is the first derivative of the M2 irradiated seeds. The result after the age of 30ADP has already showing growth and development of plants that vary when compared to its parent, both in terms of plant height, number of leaves, leaf shape and leaf forage level. In the generative phase, a plant that has been irradiated 200 and 300 gy seen some plants flower form packs, but not formed pods, there is also a form packs of flowers, but few pods produce soybean morphological characters such as plant height, number of branches, pods, days to flowering, harvesting, seed weight and seed number.

Keywords: gamma ray, genetic mutation, irradiation, soybean

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Authors: M. Kouyate, M. Sangare, S. Samake, S. Keita, H. G. Kim, D. H. Geschwind

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Background & Objectives: Human genetic studies can be expensive, even unaffordable, in developing countries, partly due to the sequencing costs. Our aim is to pilot the use of bioinformatics tools to guide scientifically valid, locally relevant, and economically sound autism genetic research in Mali. Methods: The following databases, NCBI, HGMD, and LSDB, were used to identify hot point mutations. Phenotype, transmission pattern, theoretical protein expression in the brain, the impact of the mutation on the 3D structure of the protein) were used to prioritize selected autism genes. We used the protein database, Modeller, and clustal W. Results: We found Mef2c (Gly27Ala/Leu38Gln), Pten (Thr131IIle), Prodh (Leu289Met), Nme1 (Ser120Gly), and Dhcr7 (Pro227Thr/Glu224Lys). These mutations were associated with endonucleases BseRI, NspI, PfrJS2IV, BspGI, BsaBI, and SpoDI, respectively. Gly27Ala/Leu38Gln mutations impacted the 3D structure of the Mef2c protein. Mef2c protein sequences across species showed a high percentage of similarity with a highly conserved MADS domain. Discussion: Mef2c, Pten, Prodh, Nme1, and Dhcr 7 gene mutation frequencies in the Malian population will be very informative. PCR coupled with restriction enzyme digestion can be used to screen the targeted gene mutations. Sanger sequencing will be used for confirmation only. This will cut down considerably the sequencing cost for gene-to-gene mutation screening. The knowledge of the 3D structure and potential impact of the mutations on Mef2c protein informed the protein family and altered function (ex. Leu38Gln). Conclusion & Future Work: Bio-informatics will positively impact autism research in Mali. Our approach can be applied to another neuropsychiatric disorder.

Keywords: bioinformatics, endonucleases, autism, Sanger sequencing, point mutations

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Authors: Yessengali Ussenbekov, Valery Terletskiy, Orik Zhanserkenova, Shynar Kasymbekova, Indira Beyshova, Aitkali Imanbayev, Almas Serikov

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Currently, there are 46 hereditary diseases afflicting cattle with known molecular genetic diagnostic methods developed for them. Genetic anomalies frequently occur in the Holstein cattle breeds from American and Canadian bloodlines. The data on the incidence of BLAD, CVM, DUMPS and BC autosomal recessive lethal mutations in pedigree animals are discordant, the detrimental allele incidence rates are high for the Holstein cattle breed, whereas the incidence rates of these mutations are low in some breeds or they are completely absent. Data were obtained on the basis of frozen semen of stud bulls. DNA was extracted from the semen with the DNA-Sorb-B extraction kit. The lethal mutation in the genes CD18, SLC35A3, UMP and ASS of Alatau stud bulls (N=124) was detected by polymerase chain reaction and RFLP analysis. It was established that stud bulls of the local Alatau breed were not carriers of the BLAD, CVM, DUMPS, and BC detrimental mutations. However, with a view to preventing the dissemination of hereditary diseases it is recommended to monitor the pedigree stock using molecular genetic methods.

Keywords: PCR, autosomal recessive point mutation, BLAD, CVM, DUMPS, BC, stud bulls

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Authors: Atlal El-Assaad

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Viruses change with time through mutations and result in new variants that may persist or disappear. A Mutation refers to an actual change in the virus genetic sequence, and a variant is a viral genome that may contain one or more mutations. Critical mutations may cause the virus to be more transmissible, with high disease severity, and more vulnerable to diagnostics, therapeutics, and vaccines. Thus, variants carrying such mutations may increase the risk to human health and are considered variants of concern (VOC). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - the contagious in humans, positive-sense single-stranded RNA virus that caused coronavirus disease 2019 (COVID-19) - has been studied thoroughly, and several variants were revealed across the world with their corresponding mutations. SARS-CoV-2 has four structural proteins, known as the S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins, but prior study and vaccines development focused on genetic mutations in the S protein due to its vital role in allowing the virus to attach and fuse with the membrane of a host cell. Specifically, subunit S1 catalyzes attachment, whereas subunit S2 mediates fusion. In this perspective, we studied all charged amino acid mutations of the SARS-CoV-2 viral spike protein S1 when bound to Antibody CC12.1 in a crystal structure and assessed the effect of different mutations. We generated all missense mutants of SARS-CoV-2 protein amino acids (AAs) within the SARS-CoV-2:CC12.1 complex model. To generate the family of mutants in each complex, we mutated every charged amino acid with all other charged amino acids (Lysine (K), Arginine (R), Glutamic Acid (E), and Aspartic Acid (D)) and studied the new binding of the complex after each mutation. We applied Poisson-Boltzmann electrostatic calculations feeding into free energy calculations to determine the effect of each mutation on binding. After analyzing our data, we identified charged amino acids keys for binding. Furthermore, we validated those findings against published experimental genetic data. Our results are the first to propose in silico potential life-threatening mutations of SARS-CoV-2 beyond the present mutations found in the five common variants found worldwide.

Keywords: SARS-CoV-2, variant, ionic amino acid, protein-protein interactions, missense mutation, AESOP

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Authors: Ha T. T. Ly, Truc B. Truc, Hai N. Truong, Mai P. T. Nguyen, Ngoc D. Ngo, Khanh V. Tran, Hai T. Le

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Beta thalassemia is one of the most common inherited blood disorders, which is characterized by decreased or absent in beta globin expression. Patients with Beta thalassemia whose anemia is not so severe as to necessitate transfusions are said to have thalassemia intermedia. Objective: The goal of this study is prenatal diagnosis for pregnancy woman with Beta thalassemia intermedia and her husband with Beta thalassemia carrier at high risk of Beta thalassemia major in Northern of Vietnam. Material and method: The family has a 6 years-old compound heterozygous thalassemia major for CD71/72(+A) and Hbb:c. -78A>G/nt-28(A>G) male child. The father was heterozygous for CD71/72(+A) mutation which is Beta plus type and the mother was compound heterozygosity of two different variants, namely, Hbb: c. -78A>G/nt-28(A>G) and CD26(A-G) HbE. Prenatal Beta thalassemia mutation detection in fetal DNA was carried out using multiplex Amplification-refractory mutation system ARMS-PCR and confirmed by direct Sanger-sequencing Hbb gene. Prenatal diagnoses were perfomed by amniotic fluid sampling from pregnant woman in the 16-18th week of pregnancy after the genotypes of parents of the probands were identified. Result: When amniotic fluid sample was analyzed for Beta globin gene (Hbb), we found that the genotype is heterozygous for CD71/72(+A) and CD26(A-G) HbE. This genotype is different from the 1st child of this family. Conclusion: Prenatal diagnosis helps the parents to know the genotype and the thalassemia status of the fetus, so they can have early decision on their pregnancy. Genetic diagnosis provided a useful method in diagnosis for familial members in pedigree, genetic counseling and prenatal diagnosis.

Keywords: beta thalassemia intermedia, Hbb gene, pedigree, prenatal diagnosis

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Authors: Debbarma Asis, Guha Chandan

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Tumor Protein-53 (P53) is one of the tumor suppressor proteins. P53 regulates the cell cycle that conserves stability by preventing genome mutation. It is named so as it runs as 53-kilodalton (kDa) protein on Polyacrylamide gel electrophoresis although the actual mass is 43.7 kDa. Experimental evidence has indicated that P53 cancer mutants loses tumor suppression activity and subsequently gain oncogenic activities to promote tumourigenesis. Tumor-specific DNA has recently been detected in the plasma of breast cancer patients. Detection of tumor-specific genetic materials in cancer patients may provide a unique and valuable tumor marker for diagnosis and prognosis. Commercially available MDA-468 breast cancer cell line was used for the proposed study.

Keywords: tumor protein (P53), cancer mutants, MDA-468, tumor suppressor gene

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Authors: Supachai Supmak, Yachai Limpiyakorn

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Mutation testing can be applied for the quality assessment of test cases. Prioritization of mutation test generation has been a critical element of the industry practice that would contribute to the evaluation of test cases. The industry generally delivers the product under the condition of time to the market and thus, inevitably sacrifices software testing tasks, even though many test cases are required for software verification. This paper presents an approach of applying a social network centrality measure, PageRank, to prioritize mutation test generation. The source code with the highest values of PageRank will be focused first when developing their test cases as these modules are vulnerable to defects or anomalies which may cause the consequent defects in many other associated modules. Moreover, the approach would help identify the reducible test cases in the test suite, still maintaining the same criteria as the original number of test cases.

Keywords: software testing, mutation test, network centrality measure, test case prioritization

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Authors: Dana Gabriková, Martin Mistrík, Jarmila Bernasovská, Iveta Tóthová, Jana Kisková

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The Roma (Gypsies) is a transnational minority with a high degree of consanguineous marriages. Similar to other genetically isolated founder populations, the Roma harbor a number of unique or rare genetic disorders. This paper discusses about a rare form of Charcot-Marie-Tooth disease – type 4G (CMT4G), also called Hereditary Motor and Sensory Neuropathy type Russe, an autosomal recessive disease caused by mutation private to Roma characterized by abnormally increased density of non-myelinated axons. CMT4G was originally found in Bulgarian Roma and in 2009 two putative causative mutations in the HK1 gene were identified. Since then, several cases were reported in Roma families mainly from Bulgaria and Spain. Here we present a Slovak Roma family in which CMT4G was diagnosed on the basis of clinical examination and genetic testing. This case is a further proof of the role of the HK1 gene in pathogenesis of the disease. It confirms that mutation in the HK1 gene is a common cause of autosomal recessive CMT disease in Roma and should be considered as a common part of a diagnostic procedure.

Keywords: gypsies, HK1, HSMN-Russe, rare disease

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Authors: Sanjay Kumar Parjapati, Ajai Jain

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This paper presents optimization of makespan for ‘n’ jobs and ‘m’ machines flexible job shop scheduling problem with sequence dependent setup time using genetic algorithm (GA) approach. A restart scheme has also been applied to prevent the premature convergence. Two case studies are taken into consideration. Results are obtained by considering crossover probability (pc = 0.85) and mutation probability (pm = 0.15). Five simulation runs for each case study are taken and minimum value among them is taken as optimal makespan. Results indicate that optimal makespan can be achieved with more than one sequence of jobs in a production order.

Keywords: flexible job shop, genetic algorithm, makespan, sequence dependent setup times

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Authors: Apichai Sawisit, Sirima Suvarnakuta Jantama, Sunthorn Kanchanatawee, Lonnie O. Ingram, Kaemwich Jantama

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Escherichia coli KJ122 was engineered to produce succinate from glucose using the wild type GalP for glucose uptake instead of the native phosphotransferase system (ptsI mutation). This strain ferments 10% (w/v) xylose poorly. Mutants were selected by serial transfers in AM1 mineral salts medium with 10% (w/v) xylose. Evolved mutants exhibited a similar improvement, co-fermentation of an equal mixture of xylose and glucose. One of these, AS1600a, produced 84.26±1.37 g/L succinate, equivalent to that produced by the parent (KJ122) strain from 10% glucose (85.46±1.78 g/L). AS1600a was sequenced and found to contain a mutation in galactose permease (GalP, G236D). Expressing the galP* mutation gene in KJ122ΔgalP resembled the xylose utilization phenotype of the mutant AS1600a. The strain AS1600a and KJ122ΔgalP (pLOI5746; galP*) also co-fermented a mixture of glucose, xylose, arabinose, and galactose in sugarcane bagasse hydrolysate for succinate production.

Keywords: xylose, furfural, succinate, sugarcane bagasse, E. coli

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Authors: Atitallah Sofien, Bouyahia Olfa, Attar Souleima, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

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Introduction: Ciliopathies are a spectrum of diseases that have in common a defect in the synthesis of ciliary proteins. It is a rare cause of neonatal cholestasis. Clinical presentation varies extremely, and the main affected organs are the kidneys, liver, and pancreas. Methodology: This is a descriptive case report of a newborn who was admitted for exploration of neonatal cholestasis in the Paediatric Department C at the Children’s Hospital of Tunis, where the investigations concluded with a rare genetic mutation. Results: This is the case of a newborn male with no family history of hepatic and renal diseases, born to consanguineous parents, and from a well-monitored uneventful pregnancy. He developed jaundice on the second day of life, for which he received conventional phototherapy in the neonatal intensive care unit. He was admitted at 15 days for mild bronchiolitis. On clinical examination, intense jaundice was noted with normal stool and urine colour. Initial blood work showed an elevation in conjugated bilirubin and a high gamma-glutamyl transferase level. Transaminases and prothrombin time were normal. Abdominal sonography revealed hepatomegaly, splenomegaly, and undifferentiated renal cortex with bilateral medullar micro-cysts. Kidney function tests were normal. The infant received ursodeoxycholic acid and vitamin therapy. Genetic testing showed a homozygous mutation in the DCDC2 gene that hadn’t been documented before confirming the diagnosis of renal-hepatic ciliopathy. The patient has regular follow-ups, and his conjugated bilirubin and gamma-glutamyl transferase levels have been decreasing. Conclusion: Genetic testing has revolutionized the approach to etiological diagnosis in pediatric cholestasis. It enables personalised treatment strategies to better enhance the quality of life of patients and prevent potential complications following adequate long-term monitoring.

Keywords: cholestasis, newborn, ciliopathy, DCDC2, genetic

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Authors: Ayman K. El Essawy, Amal M. Hosny, Hala M. Abu Shady

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The rapid detection of TB and drug resistance, both optimizes treatment and improves outcomes. In the current study, respiratory specimens were collected from 155 patients. Conventional susceptibility testing and MIC determination were performed for rifampicin (RIF) and isoniazid (INH). Genotype MTBDRplus assay, which is a molecular genetic assay based on the DNA-STRIP technology and specific gene sequencing with primers for rpoB, KatG, and mab-inhA genes were used to detect mutations associated with resistance to rifampicin and isoniazid. In comparison to other categories, most of rifampicin resistant (61.5%) and isoniazid resistant isolates (47.1%) were from patients relapsed in treatment. The genotypic profile (using Genotype MTBDRplus assay) of multi-drug resistant (MDR) isolates showed missing of katG wild type 1 (WT1) band and appearance of mutation band katG MUT2. For isoniazid mono-resistant isolates, 80% showed katG MUT1, 20% showed katG MUT1, and inhA MUT1, 20% showed only inhA MUT1. Accordingly, 100% of isoniazid resistant strains were detected by this assay. Out of 17 resistant strains, 16 had mutation bands for katG distinguished high resistance to isoniazid. The assay could clearly detect rifampicin resistance among 66.7% of MDR isolates that showed mutation band rpoB MUT3 while 33.3% of them were considered as unknown. One mono-resistant rifampicin isolate did not show rifampicin mutation bands by Genotype MTBDRplus assay, but it showed an unexpected mutation in Codon 531 of rpoB by DNA sequence analysis. Rifampicin resistance in this strain could be associated with a mutation in codon 531 of rpoB (based on molecular sequencing), and Genotype MTBDRplus assay could not detect the associated mutation. If the results of Genotype MTBDRplus assay and sequencing were combined, this strain shows hetero-resistance pattern. Gene sequencing of eight selected isolates, previously tested by Genotype MTBDRplus assay, could detect resistance mutations mainly in codon 315 (katG gene), position -15 in inhA promotes gene for isoniazid resistance and codon 531 (rpoB gene) for rifampicin resistance. Genotyping techniques allow distinguishing between recurrent cases of reinfection or reactivation and supports epidemiological studies.

Keywords: M. tuberculosis, rpoB, KatG, inhA, genotype MTBDRplus

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Authors: Ji Su Kim, Bo Ram Choi, Ju Yeon Cho, Hyukjin Lee

Abstract:

Epidermal growth factor receptor (EGFR) 19 deletion mutation gene is over-expressed in carcinoma patient. EGFR 19 deletion mutation is known as typical biomarker of non-small cell lung cancer (NSCLC), which one section in the coding exon 19 of EGFR is deleted. Therefore, there have been many attempts over the years to detect EGFR 19 deletion mutation for replacing conventional diagnostic method such as PCR and tissue biopsy. We developed a simple and facile detection platform based on Rolling Circle Amplification (RCA), which provides highly amplified products in isothermal amplification of the ligated DNA template. Limit of detection (~50 nM) and a faster detection time (~30 min) could be achieved by introducing RCA.

Keywords: EGFR19, cancer, diagnosis, rolling circle amplification (RCA), hydrogel

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Authors: Naser Shagerdi Esmaeli, Mohsen Hamidpour, Parisa Hasankhani Tehrani

Abstract:

Background: The TP53 mutation is frequently detected in acute myeloid leukemia (AML) patients with complex karyotype (CK), but the stability of this mutation during the clinical course remains unclear. Material and Methods: In this study, TP53 mutations were identified in 7% of 500 patients with de novo AML and 58.8% of patients with CK in Tabriz, Iran. TP53 mutations were closely associated with older age, lower white blood cell (WBC) and platelet counts, FAB M6 subtype, unfavorable-risk cytogenetics, and CK, but negatively associated with NPM1 mutation, FLT3/ITD and DNMT3A mutation. Result: Multivariate analysis demonstrated that TP53 mutation was an independent poor prognostic factor for overall survival and disease-free survival among the total cohort and the subgroup of patients with CK. A scoring system incorporating TP53 mutation and nine other prognostic factors, including age, WBC counts, cytogenetics, and gene mutations, into survival analysis proved to be very useful to stratify AML patients. Sequential study of 420 samples showed that TP53 mutations were stable during AML evolution, whereas the mutation was acquired only in 1 of the 126 TP53 wild-type patients when therapy-related AML originated from different clone emerged. Conclusion: In conclusion, TP53 mutations are associated with distinct clinic-biological features and poor prognosis in de novo AML patients and are rather stable during disease progression.

Keywords: acute myloblastic leukemia, TP53, FLT3/ITD, Iran

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Authors: Matthew T. Wilson

Abstract:

This paper covers a selection of research utilizing grammar-based genetic programming, and illustrates how context-free grammar can be used to constrain genetic programming. It focuses heavily on grammatical evolution, one of the most popular variants of grammar-based genetic programming, and the way its operators and terminals are specialized and modified from those in genetic programming. A variety of implementations of grammatical evolution for general use are covered, as well as research each focused on using grammatical evolution or grammar-based genetic programming on a single application, or to solve a specific problem, including some of the classically considered genetic programming problems, such as the Santa Fe Trail.

Keywords: context-free grammar, genetic algorithms, genetic programming, grammatical evolution

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Authors: Wafa' Alsharafat, Suhila Farhan Abu-Owida

Abstract:

Genetic algorithm (GA) is a powerful evolutionary searching technique that is used successfully to solve and optimize problems in different research areas. Genetic Algorithm (GA) considered as one of optimization methods used to solve Travel salesman Problem (TSP). The feasibility of GA in finding a TSP solution is dependent on GA operators; encoding method, population size, termination criteria, in general. In specific, crossover and its probability play a significant role in finding possible solutions for Symmetric TSP (STSP). In addition, the crossover should be determined and enhanced in term reaching optimal or at least near optimal. In this paper, we spot the light on using a modified crossover method called modified sequential constructive crossover and its impact on reaching optimal solution. To justify the relevance of a parameter value in solving the TSP, a set comparative analysis conducted on different crossover methods values.

Keywords: genetic algorithm, crossover, mutation, TSP

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Authors: Svetlana Zhikrivetskaya, Nataliya Shirokova, Roman Bikanov, Elizaveta Musatova, Yana Kovaleva, Nataliya Vetrova, Ekaterina Pomerantseva

Abstract:

Nowadays there is a growing number of couples with conceiving problems due to male or female infertility. Genetic abnormalities are responsible for about 31% of all cases of male infertility. These abnormalities include both chromosomal aberrations or aneuploidies and mutations in certain genes. Chromosomal abnormalities can be easily identified, thus the development of screening panels able to reveal genetic reasons of male infertility on gene level is of current interest. There are approximately 2,000 genes involved in male fertility that is the reason why it is very important to determine the most clinically relevant in certain population and ethnic conditions. An infertility screening panel containing 48 mutations in genes AMHR2, CFTR, DNAI1, HFE, KAL1, TSSK2 and AZF locus which are the most clinically relevant for the European population according to databases NCBI and ClinVar was designed. The aim of this research was to confirm clinic relevance of these mutations in the Russian population. Genotyping was performed in 220 patients with different types of male infertility and in 57 healthy males with normozoospermia. Mutations were identified by end-point PCR with TaqMan probes in microfluidic plates. The frequency of 5 mutations in healthy males and 13 mutations in patients with infertility was revealed and estimated. The frequency of mutation c.187C>G in HFE gene was significantly lower for healthy males (8.8%) compared with patients (17.7%) and the values for the European population according to ExAc database (13.7%) and dbSNP (17.2%). Analysis of c.3454G>C, and c.1545_1546delTA mutations in the CFTR gene revealed increased frequency (0.9 and 0.2%, respectively) in patients with infertility compared with data for the European population (0.04%, respectively (ExAc, European (Non-Finnish) and for the Aggregated Populations (0.002% (ExAc), because there is no data for European population for c.1545_1546delTA mutation. The frequency of del508 mutation (CFTR) in patients (1.59%) were lower comparing with male infertility Europeans (3.34-6.25% depending on nationality) and at the same level with healthy Europeans (1.06%, ExAc, European (Non-Finnish). Analysis of c.845G>A (HFE) mutation resulted in decreased frequency in patients (1.8%) in contrast with the European population data (5.1%, respectively, ExAc, European (Non-Finnish). Moreover, obtained data revealed no statistically significant frequency difference for c.845G>A mutation (HFE) between healthy males in the Russian and the European populations. Allele frequencies of mutations c.350G>A (CFTR), c.193A>T (HFE), c.774C>T, and c.80A>G (gene TSSK2) showed no significantly difference among patients with infertility, healthy males and Europeans. Analysis of AZF locus revealed increased frequency for AZFc microdeletion in patients with male infertility. Thereby, the new data of the allele frequencies in infertility patients in the Russian population was obtained. As well as the frequency differences of mutations associated with male infertility among patients, healthy males in the Russian population and the European one were estimated. The revealed differences showed that for high effectiveness of screening panel detecting genetically caused male infertility it is very important to consider ethnic and population characteristics of patients which will be screened.

Keywords: allele frequency, azoospermia, male infertility, mutation, population

Procedia PDF Downloads 390