Faktorfaktor genetika dalam penyakit tidak menular Yudha Nurhantari

Faktor-faktor genetika dalam penyakit tidak menular Yudha Nurhantari Bagian Ilmu Kedokteran Forensik FK UGM 2011

Materi Bahasan Peran genetika sebagai faktor Pengendalian faktor genetika

Fertilisasi Kromosom Gen Dogma sentral

GENE: A small segment of DNA that codes for the synthesis of a specific protein. Genes are located on the chromosomes. Examples: ABO blood group gene, Rh blood group gene. CHROMOSOMES: genes for the same traits, in the same order.

GENOTYPE: The specific pair of alleles present at a single locus PHENOTYPE: The clinical features or the observable characteristics of an individual determined by a pair of genes at a given locus (or genotype). The phenotype can vary following interaction with modifying genes or the environment.

What is a genetic disease? any disease that is caused by an abnormality in an individual's genome. • genetic disorders are inherited from the parents, or by acquired changes or mutations in a preexisting gene or group of genes. • Mutations occur either randomly or due to some environmental exposure. •

What are the different types of inheritance? Single gene inheritance Multifactorial inheritance Chromosome abnormalities Mitochondrial inheritance

Single gene inheritance =Mendelian = monogenetic inheritance. is caused by changes or mutations that occur in the DNA sequence of a single gene. more than 6, 000 known single-gene disorders, about 1 out of every 200 births.

Single-gene disorders are inherited in recognizable patterns: autosomal dominant, autosomal recessive, and X-linked.

Autosomal dominant Only one mutated copy of the gene is needed for a person to be affected by an autosomal dominant disorder

Autosomal recessive Is only expressed clinically in homozigote state

X‐linked dominant mutations in genes on the X chromosome

X‐Linked recessive

Y-linked mutations in genes on the Y chromosome x Y x XX XY

Some examples of monogenetic disorders include: • cystic fibrosis, • sickle cell anemia, • Marfan syndrome, • Huntington's disease, and • hemochromatosis.

Cystic fibrosis is an inherited disorder which can affect the entire body, leading to gradual disability and death. The most common symptoms are difficulty breathing and not enough enzyme production in the pancreas. Low immune system and dense mucous production lead to frequent lung infections, that are treated, but not always cured, sometimes by intravenous and oral antibiotics. Many other symptoms, like sinus infections, poor evolution, diarrhea can be effects of this disorder in the case of other parts of the body. Sometimes, recurrent lung infections during infancy or childhood may be a sign of cystic fibrosis.

Multifactorial inheritance = complex or polygenic inheritance. Multifactorial inheritance disorders are caused by a combination of environmental factors and mutations in multiple genes. Example : heart disease, hypertension, diabetes, obesity, cancers.

On a pedigree, polygenic diseases do tend to “run in families”, but the inheritance does not fit simple patterns as with Mendelian diseases. But this does not mean that the genes cannot eventually be located and studied. There is also a strong environmental component to many of them (e. g. , blood pressure).

Gout It is a genetic/acquired disorder of uric acid metabolism that leads to hyperuricemia and consequent acute and chronic arthritis. The recurrent but transient attacks of acute arthritis are triggered by the precipitation of monosodium urate crystals into joints from supersaturated body fluids which accumulate in and around the joints and other tissues causing inflammation.

Cause of gout: enzyme defects leading to overproduction of uric acid Also high dietary intake of purines as in pulses, as purines are metabolized to uric acid. Thus it has both a genetic (due to enzyme malfunction) and environmental predisposition(such as diet) and hence multifactorial.

Mitochondrial inheritance is caused by mutations in the nonchromosomal DNA of mitochondria. Mitochondria are small organelles in the cytoplasm of cells, involved in cellular respiration. Since egg cells, but not sperm cells keep their mitochondria during fertilization, mitochondrial DNA is always inherited from the female parent.

Examples of mitochondrial disease an eye disease called Leber's hereditary optic atrophy epilepsy type MERRF ( myoclonus epilepsy with Ragged Red Fibers) a form of dementia called MELAS for mitochondrial encephalopathy, lactic acidosis and stroke-like episodes.

Genetic Counseling A family health history is collected to provide information about the health of family members A diagnosis of a genetic condition may be made or confirmed in a pregnancy, after birth, in childhood or later in life. The diagnosis may be made on the basis of clinical features, biochemical tests or genetic tests

Where there is a genetic condition in a family Estimate the risks that other family members, or future children, will be affected by the condition. Discuss the impact and possible effects on the individual and their family in a supportive atmosphere. Discuss if appropriate prenatal testing and other reproductive options to ensure that any decision is made on an informed

If a genetic condition is identified by prenatal diagnosis, genetic counselling is the means by which current information and support is provided so that an inform decision can be made regarding the continuation of the pregnancy

When should genetic counselling be sought? When there is a condition that runs in a family and individuals are concerned that they or their children will develop the condition Where a previous child is affected by a serious problem in growth, development or health

Where one or more family members (blood relatives not related by marriage) have unusual features, or a serious health problem Where a woman is in her mid 30 s or older and is either planning a pregnancy or is already pregnant When a couple are blood relatives

Where an individual or their partner has some concerns about a condition in themselves or their family being passed on to their children When a fetal abnormality is detected during pregnancy When there is concern about exposure to some environmental agent such as drugs, medications, chemicals or radiation that might cause birth defects