Some disorders may confer an advantage, at least in certain in the environments. There are a number of pathways to genetic defects, the simplest of which are summarized below.
There are genetic disorders caused by the abnormal chromosome number, as in Down syndrome (three instead of two "number 21" chromosomes, therefore a total of 47).
Triplet expansion repeat mutations can cause fragile X syndrome or Huntington 's disease, by modification of gene expression or gain of function, respectively.
Defective genes are often inherited from the parents. This is often happen unexpectedly when two healthy carriers of a defective recessive gene reproduce, but can also happen when the defective gene is dominant.
Currently around 4,000 genetic disorders are quite rare and affect one person in every several thousands or millions. Cystic fibrosis is one of the most common genetic disorders; around 5% of the population of the United States carry at least one copy of the defective gene.
Terms you should know:
GENE: A small segment of DNA that codes for the synthesis of a specific protein. Examples: ABO blood group gene, Rh blood group gene.
CHROMOSOMES: genes for the same exercises, in the same order.
LOCUS: Position or location of a gene on a chromosome.
ALLELE: Refers to the different forms of a gene at one locus.
GENOTYPE: The specific pair of alleles present at a single locus. These are features seen genetically but may or may not have phenotypic (observable) characteristics.
PHENOTYPE: The clinical features or the observable characteristics of the pair of genes at a given locus (or genotype). The phenotype can vary following interaction with modifying genes or the environment.
PENETRANCE: The frequency with which individual individual carrying a given gene will show the clinical manifestations associated with the gene.
DOMINANT: A gene (allele) which is expressed clinically in the heterozygous state. In a dominant disorder only one mutant allele need be present as it covers up, or masks, the normal allele.
RECESSIVE A gene (allele) which is only expressed clinically in the homozygous state it can be suppressed if present a dominant gene and will not show it 's character in presence of a dominant gene. In a recessive disorder, both genes at a given locus must be abnormal to manifest the disorder
Types of Genetic Disorders
1 Single gene disorders including Mendelian Disorders (ie, follow mendelian order of inheritance ie Autosomal and X-linked and Y-linked) and Non-Mendelian disorders (ie, do not follow mendelian order of inheritance eg mitochondrial inheritance)
2 Multifactorial and polygenic disorders
3 Disorders with variable modes of transmission
4 Cytogenetic disorder: including autosomal disorders and sex chromosome disorders.
I]Single gene disorders
The genisis imprinting and uniparental disomy, however, may affect inheritance patterns. The divisions between recessive and dominant are not " hard and fast "though divisions between autosomal and X-linked are (related to the position of the gene).
Sickle-cell anemia is also considered a recessive condition, but carriers that have have gender for a seondre disorder, but young goats or child with two sex sistersletal disorder it by half along with the normal gene have increased immunity to malaria in early childhood, which could be described as a related dominant condition.
Subclasses of single gene disorders are as follows:
There is a 50% chance that a child will inherit the mutated gene. Conditions that are autosomal dominant have low penetration, which mutant copy is needed, a relatively small proportion of those who inherit that mutation go on to develop the disease, often later in life.
Eg Huntingtons disease, Neurofibromatosis 1, Marfan Syndrome.
Two unaffected two copies of the mutated gene (and are referred to as carriers). Eg Cystic fibrosis, Sickle cell anemia, Tay-Sachs disease, Spinal muscular atrophy. People who each carry one copy of the mutated gene have a 25%
Males are more frequently affected than females, and the chance of passing on an X-linked dominant disorders are generated mutations in genes on the X chromosome. A woman with an X-linked dominant disorder has a 50% chance of having an affected daughter Some X-linked dominant conditions, such as Aicardi Syndrome, are fatal to boys, therefore only girls have them (and boys with Klinefelter Syndrome).
Eg Hypophosphatemia, Aicardi Syndrome,
X-linked recessive disorder is also generated mutations in genes on the X chromosome. Males are more frequently affected than females, and the chance of passing on the disorder differs between men and women. With each pregnancy, a woman who carries an X-linked recessive disorder has a 50% chance of having sons who are affected and a 50 % chance of having children who carry one copy of the mutated gene.
Eg Hemophilia A, Duchenne muscular dystrophy, Color blindness, Muscular dystrophy, Androgenetic alopecia and also includes G-6-PD (Glucose-6-phosphate dehydrogenase) deficiency.
Y-linked Y-linked disorders are caused by mutations on the Y chromosome. Y-linked disorders only cause infertility, and may be circumvented with the help of some fertility treatments.
EgMale Infertility
Mitochondrial This type of inheritance, also known as maternal inheritance, applies to genes in mitochondrial DNA. Only only egg cells contribute mitochondria to the developing embryo, only females can pass on mitochondrial conditions to their children.
Eg Leber & # 39; s Hereditary Optic Neuropathy (LHON)
II]Multifactorial and polygenic disorders
Multifactoral disorders include heart disease and diabetes. Though complex problems often clustered in families, they do This makes it difficult to determine a person & # 39; s risk of inheriting or passing on these disorders.
On the pedigree, polygenic diseases do tend to "run in families", but the inheritance does not fit simple patterns as with Mendelian diseases. But this can not ever be located and studied. There is also a strong environmental component to many of them (eg, blood pressure).
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.
Also high dietary intake of purines as in pulses , as purines are metabolized to uric acid. as it both a genetic (due to enzyme malfunction) and environmental predisposition (such as diet) and hence multifactorial.
Other examples are
heart disease, hypertension, diabetes, obesity, cancers.
III]Disorders With Variable Modes of Transmission:
Some multifactorial defects are cleft lip, congenital heart defects, pyloric stenosis etc. Certain congenital malformations are either multifactorial or by a single mutant gene (that is a different class of their own).
Eg Ehlers - Danlos Syndrome: It is characterized by defects in collagen synthesis and structure the tensile strength and hence the skin is hyperextensible and the joints are hypermobile. Causes include either of the following - deficiency of the enzyme lysyl hydroxylase , deficient synthesis of type 3 collagen due to mutations in their coding genes, and deficient conversion of procollagen type 1 to collagen due to mutation in the type 1 collagen gene.
IV]Cytogenetic Disorders:
These may be from alterations in the number or structure of the chromosomes and may affect autosomes or sex chromosomes.
Eg Fragile X chromosome. It is characterized by mental retardation and an inducible cytogenetic abnormality in the X chromosome. The cytogenetic alteration is induced by certain culture conditions and is seen as a discontinuity of staining or constriction of in the long arm of the X-chromosome.
Other disorders include Down & # 39; s Syndrome in which the number of chromosomes is increased by a third "21st chromosome" and hence a total of 47 chromosomes occasion.
