[Ishani7]

Genetics is the mystery behind many non-communicable diseases today. In some cases, it is possible to analyze this using family history of genetic disorders. But this is not practical when a disease is caused by mutations. When there’s a risk for a certain disease genetically, it is better to control other factors influencing the disease. Prenatal diagnosis is used to diagnose genetic diseases at pregnancy.

Diabetes mellitus is a non-communicable disease which is widely found throughout the world. It is a multifactorial inherited disease. Environmental factors play a major role in the expression of these genes. Diabetes is classified into two types; type I which is insulin dependent Diabetes and type II which is non-insulin dependent. Onset of insulin dependent diabetes is at early childhood and type II diabetes is seen at 30-40 years.

Diabetes mellitus I is caused by autoimmune destruction of islet β cells in pancreas. This destruction of islet β cells causes insulin deficiency and deregulation of anabolism and catabolism. More than 13 different susceptible gene loci have been identified. This locus behaves as a haplotype. Later it was discovered that β polypeptide of DQ II protein which is a dimer is a part of HLA. This protein has aspartic acid in 57th position in protective or neutral alleles, If it’s replaced with a neutral amino acid like serine, alanine; they are susceptible for DM type I. Amino acid in the 57th position is important for the specificity of antigen binding. Another cause of DM type I is variable number of tandem repeats (VNTR) in the promoter region of insulin encoding gene. If VNTR’s increase, these individuals are more susceptible to type I Diabetes. Patients with DM type I has a reduced tolerance for glucose level, hyperglycemia and ketoacidosis. Type II Diabetes is the most common which is characterized by relative insulin deficiency and resistance. Hyperglycemia and hyperinsulinemia are symptoms of Diabetes type II. Persistent hyperglycemia desensitize the islet β cells such that less insulin is released for a given glucose level. Elevated basal insulin levels down regulate the insulin receptors thereby increase in insulin resistance. Glucagon is unopposed and it’s secretion increases worsening hyperglycemia. An allele at short tandem repeat variations in the intron for a transcription factor TCF7L2 is associated with type II Diabetes. It encodes a transcription factor involved in the expression of hormone glucagon which raises blood glucose concentrations.

Rheumatoid arthritis is an autoimmune disease that causes chronic inflammation of joints and also can cause inflammation of the tissues around the joints. It is a systemic illness that can last for years. It causes joint destruction and functional disability. It is commonly seen in women. Lymphocytes are activated and chemical messengers like cytokines are expressed in inflammated areas producing symptoms like swelling, stiffness of joints, tendons etc.

X linked agammaglobulinemia is a genetic disorder. This is also called as X linked hypagammaglobulinemia, Brufon syndrome. It is more commonly seen among males. Individuals with this genetic defect do not produce mature B cells, which are responsible for the production of antibodies. People with untreated XLA are prone to develop serious and even fatal infections. XLA is caused due to a mutation in X chromosome of a single gene known as Bruton’s tyrosine kinase (Btk) gene. This mutation leads to a severe block in B cell development and a reduced peripheral Ig G immunoglobulin antibody production in the serum. Btk gene is responsible for mediating B cell development and maturation, through a signaling effect on B cell receptor. It is primarily an immune deficiency disorder.

Sickle cell anemia is an autosomal recessive disorder. It is caused due to a point mutation in β polypeptide gene. Diseased people are homozygous for the sickle cell allele. Heterozygotes for sickle cell allele who are healthy but carriers; are called as sickle cell trait whereas homozygous diseased are called as sickle cell anemics. Red blood cells of diseased individuals have a characteristic property of undergoing reversible alterations in shape when subjected to changes in the partial pressure of Oxygen. RBC’s become sickle shaped instead of flat discs. In the point mutation which is a substitution of the gene encoding for β polypeptide, the 6th amino acid, Glutamic acid is substituted with Valine.

Apart from these diseases; Phenylketonuria, graft versus host disease, Neurofibromatosis, Polycystic kidney disease are among genetic factorial diseases. Environmental factors such as age, nutrition, other diseases also affect for these diseases.

[BojanaL]

Genetics behind psychiatric disorders

Genetics behind numerous somatic disorders is well known. Psychosomatic disorders, on the other hand, are not that well studied and most diseases are loosely associated with one or more genes. After genome was sequenced, number of experiments focused on psychosomatic illnesses increased drastically. Special branch of genetics, psychiatric genetics, was born with a purpose to explore genetic background of diseases such as bipolar disorder, autism, schizophrenia…It’s estimated that 1 out of 5 people in USA suffers from some kind of mental disorder while 5% have mental illness that affect their every day routine (complicate school, work and family associated duties). Dealing with mental illness is not cheap. Back in 2002, 300 billion dollars are spent just in the USA. Psychiatric genetics may bring some new insights in disease genesis and help improve both diagnostics and treatment options.

Human psychology and emotional behavior are regulated by multiple genes. One of those gene, brain derived neurotrophic factor (BDNF), is recently recognized as very important in certain mental issues. Canadian scientist Carl Ernst revealed that deletion of BDNF gene result in major depression, anxiety and obesity. Role of BDNF in brain development was already confirmed in various animal experiments. Recently conducted study of 35 000 people with mental disorders (in the Canada, USA and Europe) and 30 000 healthy controls tested significance of BDNF gene for human brain development. Five people tested for BDNF deletion showed positive result. Mutual characteristics for all adult patients were obesity, minor mental impairment, mood swings and major depression disorder. Anxiety, aggressive behavior, attention deficit disorder, obesity and mental impairment were the most prominent characteristics in children. This experiment showed for the first time that single gene could be responsible for mental disorders. Future studies will reveal whether mental condition can be improved by normalizing BDNF levels.

Schizophrenia is another severe psychiatric disorder where person loses connection with its emotions, thoughts and behavior. It affects 7 out of 1000 people (24 million people worldwide are diagnosed with schizophrenia) and it’s usually triggered between 15-35 years. Luckily, it’s treatable both pharmacologically and psychosocially. Disease is result of biological, psychological and social factors (like many psychological disorders). Genetics is strongly associated with schizophrenia development. People that have close relatives diagnosed with schizophrenia, bipolar disorder or depression are at higher risk compared to the general population. However, experiments on the twins showed that schizophrenia is not simply transmitted and triggered only genetically. When schizophrenia is confirmed in one identical twin, chances that disease will appear in other one (same genetic background) are 50%. Stressful environmental factors are the biggest trigger for the disorder. Catechol-O-methyl transferase (COMT) gene encodes an enzyme responsible for breaking down dopamine in the brain. COMT gene appears in two variants. Altered version is usually detected in people diagnosed with schizophrenia. Group of scientist from the New Zealand investigated connection between COMT gene and marijuana smoking. It was concluded that marijuana increases the chance of developing schizophrenia for 1000% if altered version of COMT gene is present in the genome. People with “normal” version of the gene didn't show any sign of schizophrenia. Another study showed that children with high predisposition for schizophrenia have 86% lower chances to develop disease if they are growing in stable and harmonic families. All together, it can be concluded that illness have genetic root, but its development is strongly affected by environmental conditions.

Autism spectrum disorder (ASD) is set of complex neurodevelopmental disorders. Main attributes of autism are stereotyped and repetitive patterns of behavior, difficulties in communication and impaired social interaction. 1 out of 88 children suffers from autism. Genetics is strongly associated with disease development. If one of the identical twins has autism, there are 36-95% chances that other twin will be sick too. Chromosomal micorarray showed that 15q part of chromosomes 15 and 16p of chromosome 16 have duplications or deletions in patients diagnosed with autism. Those regions are under extensive investigation now. What makes the quest for the right genes for autism even harder is the fact the autism is polygenic and multifaceted disease. So far, 334 genes are listed as potentially associated with autism. Scientist are hoping that combination of bioinformatics, microarray analysis and gene sequencing will brought new information in the near future and help designed better therapeutic options for affected patients.

Genetics behind a lot of psychological disorders is waiting to be revealed. Latest techniques and increased number of experiments are raising the hope that new discoveries are just behind the corner, as well as therapeutics that could improve life of the patients suffering from various kind of metal impairment.