Biology XII:5 Prin of Inher & Vari(8 Mutation)

Mutation, Pedigree Analysis, & Genetic Disorders   Mutation Alteration of DNA sequence resulting in changes in genotype and phenotype of organisms DNA helix runs in a chromatid, hence any change (insertion or deletion) in the DNA sequence affects the chromosome. Point Mutation − Mutation arising due to change in single base pair of DNA as in sickle cell anaemia Frameshift Mutation − Mutations arising due to deletion or insertion in DNA sequence Mutagens − Chemical or physical agents that lead to mutationsExample − UV radiations Pedigree Analysis Pedigree analysis is the analysis of inheritance of traits in several generations of a family. A particular trait under study is represented in a family tree. By using pedigree analysis, inheritance of a specific trait, abnormality or disease, can be traced. DNA is believed to be the carrier of genetic information, which passes unaltered from generation to generation. Mutations occasionally alter the genetic material and genetic diseases are believed to be associated with these alterations only. Standard symbols in pedigree analysis are as follows: Pedigree chart is represented as follows: Chart (a) represents inheritance of an autosomal dominant trait as in muscular dystrophy.Chart (b) represents inheritance of an autosomal recessive trait as in sickle cell anaemia. Genetic Disorders Include Mendelian disorders and chromosomal disorders Mendelian Disorders Characterized by mutation in a single gene Their mode of inheritance follows the principles of Mendelian genetics. Mendelian disorders can be autosomal dominant (muscular dystrophy) autosomal recessive (sickle cell anaemia) sex linked (haemophilia) Haemophilia Sex-linked recessive disease Transmission − From unaffected female (carrier) to male progeny Females act as carriers of disease, but rarely suffer from haemophilia since for a female to become haemophilic, the mother should be carrier and father should be haemophilic. In this disease, protein involved in blood clotting is affected. Therefore, even a simple cut results in uncontrolled bleeding. Sickle cell anaemia Autosomal recessive disease Transmission − From parent to offspring when both parents are carriers of disease Pair of alleles HbA and HbS controls the expression of this disease.HbA and HbA − NormalHbA and HbS − Carrier of diseaseHbS and HbS − Diseased Cause of the disease − Change in gene causes the replacement of GAG by GUG leading to the substitution of Glu by Val at sixth position of beta globin chain of haemoglobin. The mutant haemoglobin so formed polymerises at low oxygen tension, resulting in change in shape of RBC to sickle-like. Phenylketonuria Autosomal recessive disease Phenylalanine TyrosineThe enzyme responsible for this conversion gets mutated. Phenylalanine accumulates. Then,Phenylalanine → Phenylpyruvic acid → Accumulates in brain → Mental retardation Phenylpyruvic acid also gets excreted through urine since kidneys poorly reabsorb it. Chromosomal Disorders Total number of chromosomes in humans = 46 (23 pairs) Total 23 pairs = Autosomes (22 pairs) + Sex chromosomes (1 pair) Monosomy − Lack of any one pair of chromosomes Trisomy − Inclusion of an additional copy of chromosomes Aneuploidy − Loss or gain of chromosomes due to failure of segregation of chromatids during cell division