New Loci for Genetic Resistance to Malaria in Humans - Essay Example

New Loci for Genetic Resistance to Malaria in Humans Murray approximates the fatal cases of malaria to one million deaths annually, with most of the victims being African children. This makes it a leading cause of disease-related fatalities in the world. Factors dictating the susceptibility of malaria include environmental, parasite virulence and host genetics (Mackinnon et al., 2005). These facts may interplay to determine the cause of the disease. The condition is a product of protozoan parasites of genus Plasmodium. The pathogenic species belonging to this genus include P. ovale, P. Malariae, P. falciparum, P. vivax and P. Knowlesi. The severe form of the condition is the one caused by P. falcipurum which is prevalent in the Sub-Saharan Africa. Some overlapping clinical syndromes that indicates the severe form includes severe anaemia (SA) and cerebral malaria (CM) (World Health Organisation, 2000). The essay below refers to GWAS approach to develop the strategies applied in the development of control for infectious diseases in humans. According to Kwiatkowski (2005), the disease has been identified as a potent type in the human population. This is because genetic traits such as sickle cell variants have been proven to protect people from malaria. Some highly variant genes offer resistance to malaria e.g. sickle cell haemoglobin variant (Hb-S) and Glucose-6-phosphate dehydrogenase (G6PDH). This affirms that malaria resistance among humans is genetic (Hedrick, 2011). The response to the malarial parasite of the human body varies i.e. some people may succumb upon infection while others may survive. This variation is caused by genetic factors (Mackinnon et al., 2005). The prevalence of the disease has led to an increase in mutation in the human body to counter the negative effects of the disease. Snow et al., (2005) alludes that the malaria form caused by P. falcipurum in endemic areas has led to a strong selective pressure among the human population. According to Mangano and Modiano, (2009), malarial severity differs due to mutations that occur in the erythrocytes harbouring the malaria parasite in the vital pathogenesis. These mutations affect the nitric oxide metabolism, production and maturation of malarial parasites. For instance, the severe malaria is modulated by rate limiting enzyme haemoxygenase I (HO-1). Studies on the genetic make-up of the human body have been enhanced by construction of a complete human genome. Enhanced genomic studies have been conducted globally to understand the variant traits of diseases and conditions such as diabetes and/or malaria. The genome wide studies include studies related to genome linkage and association. Genome-wide association studies are involved in the identification of the pathways influencing malaria, especially the severe form of malaria. Human chromosome 10 (10p15.3-14) and chromosome 13 (13q) have been identified by Timmann et al. (2012) to possess pronounced linkages to the severe malaria forms. Genome-wide association studies links individuals with common genetic variants to a host of diseases and traits. Hirschorn and Daly (2005) deduce that the studies are characterised by a survey across the genome sets of Single Nucleotide Polymorphism (SNP) for most of the common genetic variation that causes diseases or exposes an individual to disease vulnerability. Additionally, these studies contribute in the identification of the variants contributing to the disease on focus. The genome-wide analysis identifies the factors that influence health and disease. Contrary to the linkage studies where markers associated with the genome must segregate with diseases in families, the GWAS studies focuses on the analysis of genome for possible genetic variants causing the disease (Hirschorn and Daly, 2005). Timmann et al., (2012) asserts that resistance to malaria has not been comprehensively established. The GWAS studies are appropriate for identifying the variants for the genetic resistance in the body. The GWAS studies involve the application of theoretical knowledge related to the disease under study. The ability to genotype comprehensively is also crucial because as Kruglyak and Nickerson (2001) asserts, there are over one million SNPs contained in the dbSNP database representing the human genome. The GWAS studies use various markers, one of them being linkage disequilibrium-based markers (LD-based markers). Jorde (2000) portend that these markers are strongly related to the allele that causes the disease. Effective GWAS studies require large samples of the markers as they are more resourceful in multiple populations. Small sample sizes may lack the required statistical power leading go reduced association. Additionally, there is low analytical power in small samples due to low allele frequency. The GWAS study groups together the overlapping symptoms of the falciparum malaria during pathogenesis in setting-up appropriate controls. The project, dubbed Severe Malaria in African Children (SMAC) was conducted in three phases; GWAS, group and replication. The process involved sequencing and analysing two genes for the presence of SNPs. The sample composed of 1,500 patients with both the cerebral malaria and severe anaemia as well as 1,000 control children. The sample also contained 1325 individuals with various illnesses such as severe anaemia (n=916), cerebral malaria (n=280) or both forms (n=129) as well as people with respiratory distress and concomitant signs/symptoms of severe malaria were included in the study. The concomitant signs/symptoms of malaria included hyperlactataemia, hypoglycaemia and prostration among others. The GWA cases had a median age on 28 months, 53% of these comprised of males. The replication group was composed of 1320 cases, with the severe malaria portraying overlapping symptoms. The two genes sequenced in this project included the ATP2B4 and MARVELD3. The study posits that the genotype was carried out using human SNP array 6.0 as well as the stringent quality control with the imputation being carried by the MACH software. The genotype data of 174 individuals included in the 1000 genomes project, 2010-08 release comprised the imputation. The SNPs were more than 5 million in number. On the other hand, the HapMap project involved the inclusion of over 300 million genotypes. The project stems in numerous countries including the United Kingdom, United States and Nigeria. The project aims to identify the genetic diversity among human beings. The genetic information includes the various responses to medication and environmental pressure by genetically different individuals (International HapMap Project, n.d.). Through the application of thresholds of P 0.05 and P Read More