For many years counting cells and identifying them under the microscope has been the conventional method to determine the number of abnormal and normal cells in cancers. During the last decade, studies have shown that the detection and quantification of residual tumor cells is important in predicting the clinical outcome of several types of hematological malignancies. Detection of
minimal residual disease (MRD) is now becoming routinely implemented in treatment protocols and is increasingly used for guiding therapy and for evaluation of new treatment modalities (Raanani & Hashomer, 2004). A wide variety of techniques have been developed to detect residual malignant cells beyond the sensitivity of conventional approaches by cell morphology. One of these technology is by real time quantitative (RQ) polymerase chain reaction (PCR) using the Taqman and LightCycler systems.
The multi-racial, multi-lingual, multi-religious, and multi-cultural Malaysia is situated at the crossroads of Southeast Asia. It has a total population of about 23 million, comprising of more than fifty ethnic groups: Malays, Chinese, Indian, and the minorities of Orang Asli in Peninsular; Iban, Bidayuh, Melanau, Kenyah Kayan, Ukit, Penan, Sekapan, Lahanan, Lun Bawang, Kelabit, Berawan, Punan Bah etc. in Sarawak; and Kadazan, Bajau, Murut, Paitan, Suluk Bonggi, Illanun, Bengkahak Tidung etc. in Sabah. The origin of the multi-ethnic character of this country traces back to decades of human migration from various regions of Southeast Asia. With her rich human biodiversity, a study of the human population genetics is imperative, either for forensic database purposes, or as the stepping stone for medical applications.
In the human genome, point variations are most common (Nachman & Crowell, 2000) and well understood. These variations, when existing in more than 1% of the population, is referred to as
Single Nucleotide Polymorphism (SNP) and can fall in the coding region of a gene, non coding region or intergenic regions.
Spinal muscular atrophy (SMA), a leading genetic cause of death in childhood, is caused by deletion of the SMN1 gene, located at chromosome 5q13. The molecular pathogenesis, which results in motor neuron degeneration within the anterior horn of spinal cord, is a focus of debate among scientists. The unique nature of the duplicative 5q chromosomal region provides considerable yet challenging opportunity for disease correction as well as complication in performing molecular diagnosis and understanding the molecular pathogenesis. This article reviewed recent findings in the molecular pathogenesis of SMA as well as the research advances in the molecular diagnosis and therapeutic approaches.
The telomere and telomerase hypothesis of aging and cancer is based on the findings that most human tumors have telomerase activity while almost all normal human somatic cells do not. Telomeres are nucleoprotein structure that located 100-300 kb from the end of linear eukaryotic chromosomes (Blackburn et al, 2001; Yoo & Robinson, 2000). Human telomeres consist of thousand repetitive sequences TTAGGG with ranging from 5 to 20 kb (Figure 1) (Martin, 2002). In human cell, there are 92 telomeres which have several functions including protecting chromosome ends, to maintain chromosome stability, serve as an attachment point to the nuclear matrix and also involve in the cell replication.
The splicing of the pre-mRNA is one of the most essential and one of the several processes that characterized the exponential enrichment of proteomic diversity in higher eukaryotic organisms (Black, 2000, Graveley, 2001). For the splicing process, the introns must be removed and this is accurately carried out by an assembly of spliceosome
Rheumatoid Arthritis (RA) is a chronic inflammatory polyarthritis disease predominantly involving synovial tissue of the joints and characterized by destructive and debilitating arthritis (Choy et al., 2012; Weyand, 2000; reviewed by Worthington, 2005; Gabriel et al., 1999). It can cause progressive and irreversible destruction of tendons, cartilage and bone, which leads to lack of ability to perform daily activities (Singh et al., 2015). Although the aetiology of RA remains unsolved, the strength of the genetic component in RA is estimated based on familial aggregation and information about epidemiology and population prevalence (reviewed by Gregersen, 1999, Choy et al., 2012). (Copied from article).
In various biological studies, for example those in population genetics, conservation biology, forensic science, gene mapping, breed, strain and population characterization and identification, marker assisted selection and the identification of cryptic species complexes, codominant genetic markers play important roles. The information that can be gained from them are far superior than those from dominant markers like random amplified polymorphic DNA (RAPD), amplified fragment length polymorphisms (AFLP), direct amplification of length polymorphisms (DALP) and randomly amplified microsatellites (RAM) or inter simple sequence repeats (ISSR).
The genetic relationship between any two populations is a function of the differences between them in allele frequencies, with this relationship commonly expressed in terms of a genetic distance. For example if the two populations are homozygous for different alleles at a particular locus, the distance is the maximum possible whereas if the allele frequencies in the two populations are identical, the distance is zero. The estimated genetic distances may vary among loci. Thus, the most accurate measures of relationships will be obtained by averaging many loci (Nei, 1978). In plant and animal breeding, it is expected that a cross between two individuals originating from two populations with a large genetic distance between them will result in maximum heterosis or hybrid vigour. Many estimates of genetic distances are available in the literature but Nei’s standard genetic distance, D, (Nei, 1972, 1978) had been extensively used in studies of human, animal and plant varieties, races, breeds, strains, populations, species and genera.
Malaysia, with her tropical jungles, mangroves and seas, is blessed with riches in biodiversity, being one of the twelve megabiodiversity countries on earth. Genetics has contributed substantially to the success of our country's agricultural production especially of rubber and palm oil. Hence, it should play a pivotal role in helping Malaysia fulfill her responsibility to identify, characterize and sustainably utilize her numerous indigenous bioresources for the benefit of humanity.
The world’s biodiversity is not distributed uniformly throughout the globe. Some areas such as the tropical rainforests, seas and coral reefs teem with the varieties of life whereas others such as some deserts and polar regions are almost devoid of them (Gaston, 2000). Malaysia, with her tropical jungles and seas, is rich with biodiversity. She is fortunate to have had eminent pioneers such as Ridley (1967), Corner (1972), Soepadmo (1972) and Whitmore (1983) to study her flora and Medway (1968) and Lim (1991) to study her fauna taxonomy. Other pioneers in Malaysian biology included Berry, Dhaliwal and Mohsin. These pioneers are then ably followed by workers such as Latiff, Kiew, Go, Khoo, Davidson, Saberi, Omar, Jambari, Idris, Zekri, Teo, Marziah, Tan, Mukherjee, Shapor, Yusoff, Azmi and many others studying the various subdisciplines of biology. In addition to the more obvious large plants and animals, microorganisms and aquatic organisms had not been neglected either. Workers such as Nawawi, Verghese, Ho and Faridah are known
for their work on fungi while Fatimah, Phang, Japar and Anton had studied algae, seaweeds, diatoms and seagrasses. However, some of these workers have now either retired or are soon going to attain retirement age and the worrying part is that there are not many younger
workers keen to pursue research in taxonomy and biosystematics, a prerequisite to further studies in ecology, genetics, biotechnology which in turn are prerequisites for rational conservation, management and sustainable utilization of our rich biological resources. With each passing day species are becoming extinct sometimes without us even knowing that they had ever existed. Even in a developed country such as the USA, one third of her plant and animal species are at risk of extinction (McCann, 2000). Hence, taxonomic and biosystematic studies of our plants, animals and microbes whether terrestrial or aquatic, freshwater and marine, should be priority areas. So should studies on their reproductive biology, life cycles, physiology, feeding habits, migration patterns, predators and their sensitivities to environmental changes.
This paper describes the first reported attempt to isolate DNA sequences containing repeat motifs in Eurycoma longifolia and Orthosiphon stamineus. A library enriched for genomic repeat motifs was developed using novel oligonucleotides designed with inosine residues incorporated at predetermined positions. A total of eight and twelve specific molecular markers were developed for O. stamineus and E. longifolia respectively. These markers have a potential application in estimating population diversity levels and QTL mapping in these two medicinal plants, which are widely used in the Malaysian herbal industry.
In Malaysia, harmful algal blooms often occur along the coastal waters of west Sabah, where one of the causative organisms is the toxin-producing dinoflagellate, Pyrodinium bahamense var. compressum. A total of five P. bahamense var. compressum isolates were obtained from four locations and were cultured in f/2 medium. A Polymerase Chain Reaction (PCR) based technique was developed and used to screen for the presence of the dinoflagellate, P. bahamense var. compressum. A dinoflagellate-specific primer pair was designed based on sequences of P. bahamense var. compressum to amplify the 18S small subunit ribosomal DNA (rDNA) sequences. The rDNA of the P. bahamense var. compressum isolates were obtained. A species-specific primer pair was designed to target a 600 bp rDNA sequence of the target dinoflagellate. The primer pair targeting P. bahamense var. compressum did not yield any product with the fifteen algae cultures used as negative controls, but only amplified the rDNA of P. bahamense var. compressum cultures. The PCR method for identification of P. bahamense var. compressum was also applied on twenty field samples collected with plankton net. P. bahamense var. compressum cells were detected by PCR in five field samples and were confirmed by direct sequencing. From this study, a species-specific primer pair was obtained to identify the target species, P. bahamense var. compressum, among the natural complex communities of seawater.
Electrophoresis is a crucial step for the studies of proteins, allozymes, DNAs and RNAs. Two commonly used electrophoresis systems are agarose gel and polyacrylmide gel. Agarose gel is frequently used for DNAs and RNAs studies whereas polyacrylmide gel is widely used for the studies of other macromolecules such as proteins, allozymes (isozymes), DNAs and RNAs. The banding patterns of the gels, rather than the numbers of bands appearing on the gels are important for scoring in fingerprinting, footprinting and in population genetic studies.
The blood of the Painted Storks (Mycteria leucocephala) and the Milky Storks (M. cinerea) from Malaysia were collected
invasively from the breeding site. The blood was dropped on to FTA® cards and stored at room temperature. DNA was isolated from
the FTA® cards through a modification of the Wizard DNA Purification kit (Promega) procedure and PCR was performed with 11 pairs
of microsatellite primers of the American Wood Stork (M. americana). The collection of a drop of blood onto the card is superior to the
usual practice of collecting about five ml of blood into a vacuum tube as it causes fewer traumas to these sensitive birds. Moreover, this
collection procedure can be adopted for use in various wild animal species which are usually found in the remote areas of Malaysia as
the sample collection cards can be transported back to the laboratory at room temperature. Our procedure allows the typing of several
molecular genetic markers from just a drop of blood collected in the field and stored at room temperature alleviating the need for storage
in expensive deep freezers or liquid nitrogen tanks.
Resistance to anti-HER2 targeted therapy imposes a crucial limitation to the successful treatment of HER2 positive breast cancer. The expression of HER4 and its prognostic value is controversial in breast cancer. The role of HER4 in trastuzumab treatment and resistance in HER2-positive breast cancer has been recently studied. HER4 activation, cleavage and nuclear translocation have been demonstrated mediate trastuzumab resistance in HER2 positive breast cancer. In addition, nuclear HER4 is suggested could be a novel predictive and prognostic biomarker in HER2 positive breast cancer patients. Understanding the role of HER4 may offer useful insights to cancer treatment in HER2-positive breast cancer and other cancers.
Telomerase has become important in molecular genetics since its discovery in 1984. The study of telomere in ciliate Tetrahymena thermophilia since 4 decades ago has led to the discovery of telomerase that was discovered by Elizabeth Blackburn and her postgraduate student, Carol Widney Greider in 1984. Later in 2009, Jack William Szostak together with Greider and Blackburn were awarded the Nobel Prize in Physiology or Medicine for their discovery. (Copied from article).
Orofacial clefts are one of the most common congenital malformations among newborns. The two main types of oral clefts are cleft lip with or without cleft (CLP) and cleft palate alone (CP). Cleft is an abnormal ssure in an anatomical structure that is normally fused. Cleft lip is the congenital failure of the maxillary and medial nasal processes to fuse, forming a ssure in the lip. Cleft palate is the congenital failure of the palate to fuse properly, forming a ssure in the roof of the mouth (Mossey, 2009).clefts are one of the most common congenital malformations among newborns. The two main types of oral clefts are cleft lip with or without cleft (CLP) and cleft palate alone (CP). Cleft is an abnormal ssure in an anatomical structure that is normally fused. Cleft lip is the congenital failure of the maxillary and medial nasal processes to fuse, forming a ssure in the lip. Cleft palate is the congenital failure of the palate to fuse properly, forming a ssure in the roof of the mouth (Mossey, 2009).
Smaller family size and advancing parental age have increased the demand for prenatal diagnosis.
Prenatal cytogenetic diagnoses currently used, such as amniocentesis and chorionic villus
sampling, are usually not preferred by the expectant couples due to the risk imposed on the mother and child. High false positive rates (5%) of current non-invasive screening methods, such as serum analysts or ultrasound, cause a large number of unnecessary invasive practices to be performed, which apart from the associated risk, place considerable psychological distress on the couples
involved (Wald et al., 1999). (Copied from article).
The Malaysian fish production is about 1.5 million metric tonnes and 86.9% of this comes from the marine sector and 13.1% from the inland sector. This included fish production by capture and culture. (DOF, 2002). Fisheries genetic resources need to have a value in terms of economic, ecological and social uses and they need to characterized. This is the mandate to FAO and it is also necessary for fisheries management and aquaculture development. The vast aquatic diversity that exists in Malaysia consist of numerous taxa of marine and freshwater fishes, crustaceans, mollusks, plants and animals. These figures could be an underestimate to the actual figure. The levels of genetic diversity includes ecosystems, communities, population, genotypes and individual genes. A knowledge of the genetic background of a species and its population structure is essential for its management, breeding and conservation programmes in fisheries. Problems like how to choose the right candidates for breeding, identifiying and monitoring lines, families and individuals, monitoring and control of inbreeding, inheritance of simple traits and genetic improvement through selection for favourable gene and gene combinations can potentially be answered through the use of molecular markers in the management of fisheries genetic resources.