GENETIC DISORDERS

Genetic disorder are due to inherited defect in chromosomes or genes.

Chromosome

   A linear thread in the nucleus of a cell. It contains the DNA, which transmits genetic information. They contain the gene or hereditary determiners.

Gene

The basic unit of heredity. Each gene occupies a certain location on a chromosomes attached end to end in DNA.

nA pair of gene on DNA control the appearance of a given characteristics and situated at a specific sites / locus

nEach gene of a pair is allele.

nIf allele is identical: Homozygous.

nIf allele is different: Heterozygous.

nMay be dominant or may be recessive.

nGenotype: Genetic constitution.

nPhenotype: Manifestations of genotype.

Mutation: A mutation may be defined as a permanent change in the DNA.

  Types:

n Genome mutation: Loss or gain of whole chromosome eg: monosomy, trisomy.

nChromosome mutation: involve number or structure.

nGene mutation: Results in partial or complete deletion of a gene or more commonly a single nucleotide base.

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nPoint mutation: Single nucleotide base is substituted by a different base resulting point mutation.

nFrame shift mutation: One or more bases are inserted into or deleted from the DNA.

Causes:

nSpontaneous mutation: Mutation occurs spontaneously during DNA synthesis

nMutagens: Certain environmental factors increase the rate of spontaneous mutations or induce mutation.

1.Physical mutagens: UV rays, Ionizing radiation

2.Chemical mutagens: Anti-cancer drug like methotraxate

3.Virus:Rubella Virus

   Classification:

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nMendelian disorder

nMultifactorial disorder

nSingle gene disorder with non-classic inheritance

nChromosomal ( cytogenetic disorder) 

 DIAGNOSIS:

nCytogenetic analysis:

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nPrenatal performed on fetal cell obtained by amniocentesis (16 Week) chorionic villous biopsy ( 8-10 Week)

nPost natal peripheral lymphocytes

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nComplete chromosome study ( Karyotype)

nBarr body X chromatin/sex chromatin body 

Molecular analysis:

nGenetic engineering by  using recombient DNA technology for DNA diagnosis.

nDirect gene diagnosis: involve detection of mutant gene.

nGene tracking: Indirect gene diagnosis- detection of linkage of the disease gene with a harmless marker gene.

nRELP (restriction fragment length pleomorphism)

nVNTR (variable number of tandem repeats)

Indication of cytogenetic analysis

Genetic disorder

Prenatal: Performed on fetal cells obtained by amniocentesis or chorionic villus biopsy.

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nAdvanced maternal age (>34 years)

nA patient with a structural chromosomal abnormality (eg. Robertsonian translocation)

nPrevious child with chromosomal abnormality

nA parent who is carrier of an X-linked disease ( to determine fetal sex).

   Postnatal: Performed on peripheral blood lymphocytes.

nMultiple congenital abnormality

nUnexplained maternal retardation

nSuspected chromosomal abnormality

nSuspected fragile x syndrome

nInfertility, to exclude sex chromosomal abnormality

nRecurrent abortion (both parents must be evaluated to rule out carriers of balanced translocation). 

Anaemia: http://anaemiaofhuman.blogspot.com/

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