- Dr. Gourav Thakre Jr-3 Dept. Of AnatomyDr.S.C.G.M.C. Nanded
Mode of inheritance “ It Describes the different ways in which genes handed down from parents to their offspring through several generations may express themselves.”
Genetic disorders classified into: Chromosomal disorders: abnormality in the number or structure of chromosomes. Single gene disorders: called as Mendelian disorders, due to a single mutant gene. Four basic pattern of inheritance. Multifactorial inheritance: disorder is a result of interaction of gene and environmental factors. Mitochondrial disorders: some neuropathies
Analysis of Genetic disorderWhile dealing with genetic case:1) Recording family history of the index case.2) Index case/ proband: is an affected person who has bought the attention of the family to the clinician.3) Also called as propositus or proposita if female.4) All the information is taken abt. Proband.5) In family history – does any of relative has similar complaints. - does any relative show any other disease which is not present in proband. - any condition with which any of the relative has suffered or is suffering which might have been unnoticed.
6) Is proband an outcome of consanguineous marriage?7) What is the ethnic group of the family?8) Record addresses of the relevant family members as this is very important in order to contact them.
Terminology Allele or Allelomorph : One or more alternative forms of a gene found at the same (corresponding) locus on homologous chromosomes in an individual &/or a population. Homologous genes: Identical alleles occupying the same locus on homologous chromosomes.
Homozygous : An individual (homozygote) who possesses two identical alleles at one particular locus on homologous chromosomes. Heterozygous: An individual (heterozygote) who possesses two different alleles at one particular locus on homologous chromosomes.
Dominant: An allele that is always expressed, both in homozygous and heterozygous conditions Recessive: An allele that is expressed only when it is homozygous.
Genotype: The total genetic constitution (genome) of an individual, or more specifically ,the alleles present at one locus for a particular trait. Phenotype: The appearance (physical, biochemical & physiological) of an individual produced by expression of the genotype under the influence of the environment.
Pedigree Depicts the family data. Shorthand method of giving relevant information. Also the mode of transmission of the disorder in the family.
Punnett square The Punnett square is a diagram that is used to predict an outcome of a particular cross or breeding experiment. Reginald C. Punnett To determine the probability of an offsprings having a particular genotype.
Mendelian Inheritance Caused by single mutanat gene. Follow one of the following four pattern of inheritance. - Autosomal Dominant. - Autosomal Recessive - Sex/ X- linked Dominant - X- linked Recessive inheritance.
Sex - linked inheritance Sex linked inheritance means X – linked or Y- linked inheritannce. Genes on Y chromosome shows holandric inheritance. Y chromosome has H – Y gene which shows single gene mutation and trait is hairy pinna. So sex – linked inheritance means X – linked . It can be either Recessive or Dominant.
X – linked recessive inheritance. Males are said to be hemizygous in respect to X – linked gene. The trait is determined by the gene carried on X – chromosome. It manifests in females only when it is in double dose therefore females are rarely affected. A heterozygous female forms a carrier. In males even single mutant gene on their X- chromosome (heterozygous state) are affected.
Examples of X – linked recessive traits Haemophilia. Duchenne muscular dystrophy. Colour blindness. G6PD deficiency.
Duchenne muscular dystrophyX – linked recessive trait, characterized by progressive muscular weakness. Incidence : 1 in 3500 males. Clinical features : - present between 3 to 5 years. -muscular weakness characterized by awkward gait, difficulty in climbing and inability to run. -while standing from sitting position the child climbs on itself, called as Grower’s sign.
-Lumbar lordosis in advanced cases. -Inability to walk by the age of 11 years. -Death, age ~20 from respiratory infection or cardiac failure DMD gene on the end of X chromosome Encodes protein dystrophin that supports plasma membrane during contraction If dystrophin absent or defective, cells are torn apart Diagnosis : elevated creatine kinase in serum. muscle biopsy.
Haemophilia - ADeficiency of factor VIII in bloodIncidence – 1 in 5000- 10,000Clinical features: Increased prolonged bleeding Hemorrhages in joints and muscles Intracranial bleedingCytogenetics: Distal region on long arm of chromosome X.186kb DNA & 26 exons.
Colour blindness Inability to perceive the colour Green (deuteranopia) & Red (protanopia) Incidence: 1-8 %Cytogenetics : Distal portion of long arm of chromosome X Genes for red & green opsin proteins are located adjacent to each other Deletion of genes Unequal crossing over in meiosis.
X – linked dominant inheritance X – linked dominant trait occurs more frequently in females. Twice common in females than males. Affected male transmits the trait to all his daughters and none to his sons. Examples : -vitamin D resistant rickets. -Hypophosphataemia. -Alports syndrome. -charcot marie tooth disease.