BBT419
Clinical Biochemistry & Xenobiotics
SPRING-2025
TOPIC-03 | Lecture 9-12
. . .
, Genetic Basis of Disease
. . .
Terminologies
Gene .- .Functional .unit .of .chromosomes
Locus .- .Physical .location .of .gene .in .chromosome
. Alleles .- .Duplication .of .a .gene .in .paired .chromosomes ./
. Variant .form .of .a .given .gene
Genotype .- .Genetic .makeup .of .an .individual
. Phenotype .- .Physically .recognizable .character .of .the
. genotype
Dominant .- .Character .expressed .due .to .one .allele
. Recessive .- .Character .expressed .due .to .both .the .alleles
. Homozygous .- .Similar .type .in .both .the .alleles
. Heterozygous .- .If .the .allele .possess .different .characters
. Autosomal .- .Related .to .normal .body .cells
Sex-linked .- .Related .to .germ .cells
, Genetic Basis of Disease
. . .
Mutation- Transmittable change in genetic material
. . . . .
Qualitative .e.g., .HbS
Quantitative .e.g., .Insulin .in .type .1 .diabetes
Visible .- .Effects .expressed .physically .e.g., .Defective .skin, .pigments
Hidden .– .Affected .individual .with .no .expression .of .defect
Sometimes advantageous
.
In .HbS .heterozygotes- .no .malarial .disease .as .Plasmodium .falciparum .cannot .grow.
Qualitative Mutation
.
AA .composition .and .Protein .function .altered .without .affecting .the .gene
. expression .level.
HbS .Single .Point .Mutation .(AT) .Changes .E(GAG)V(GTG) .at .codon .6 .of .β-
. globin .gene.
, Genetic Basis of Disease
. . .
The four types of inherited genetic disorders
. . . . . .
Single gene inheritance (disorders of a single gene)
. . . . . . .
Mendelian .or .monogenetic .inheritance .Single .gene .affected
Have .different .patterns .of .genetic .inheritance .- .AD, .AR, .XLD, .XLR
Multifactorial inheritance .
complex .or .polygenic .inheritance
combination .of .environmental .factors .and .mutations .in .multiple .genes,
e.g., .Breast .Cancer . .Mutations .in .Chr .6, .11, .13, .14, .15, .17, .22
Chromosome abnormalities .
Numerical .Disorder, .Trisomy .21,18,13, .Turner, .Klinefelter
Structural .Disorder, .Cri-du-chat .(46,XX .or .XY, .5p-)
Mitochondrial inheritance .
mutations .in .the .non-nuclear .DNA .of .mitochondria
Each .mitochondrion .may .contain .5 .to .10 .circular .pieces .of .DNA
mitochondrial .DNA .is .always .inherited .from .the .maternal .parent.
Leber's .hereditary .optic .atrophy, .mitochondrial .encephalopathy, .lactic .acidosis, .and .stroke-like
.episodes .(MELAS), .myoclonic .epilepsy
Clinical Biochemistry & Xenobiotics
SPRING-2025
TOPIC-03 | Lecture 9-12
. . .
, Genetic Basis of Disease
. . .
Terminologies
Gene .- .Functional .unit .of .chromosomes
Locus .- .Physical .location .of .gene .in .chromosome
. Alleles .- .Duplication .of .a .gene .in .paired .chromosomes ./
. Variant .form .of .a .given .gene
Genotype .- .Genetic .makeup .of .an .individual
. Phenotype .- .Physically .recognizable .character .of .the
. genotype
Dominant .- .Character .expressed .due .to .one .allele
. Recessive .- .Character .expressed .due .to .both .the .alleles
. Homozygous .- .Similar .type .in .both .the .alleles
. Heterozygous .- .If .the .allele .possess .different .characters
. Autosomal .- .Related .to .normal .body .cells
Sex-linked .- .Related .to .germ .cells
, Genetic Basis of Disease
. . .
Mutation- Transmittable change in genetic material
. . . . .
Qualitative .e.g., .HbS
Quantitative .e.g., .Insulin .in .type .1 .diabetes
Visible .- .Effects .expressed .physically .e.g., .Defective .skin, .pigments
Hidden .– .Affected .individual .with .no .expression .of .defect
Sometimes advantageous
.
In .HbS .heterozygotes- .no .malarial .disease .as .Plasmodium .falciparum .cannot .grow.
Qualitative Mutation
.
AA .composition .and .Protein .function .altered .without .affecting .the .gene
. expression .level.
HbS .Single .Point .Mutation .(AT) .Changes .E(GAG)V(GTG) .at .codon .6 .of .β-
. globin .gene.
, Genetic Basis of Disease
. . .
The four types of inherited genetic disorders
. . . . . .
Single gene inheritance (disorders of a single gene)
. . . . . . .
Mendelian .or .monogenetic .inheritance .Single .gene .affected
Have .different .patterns .of .genetic .inheritance .- .AD, .AR, .XLD, .XLR
Multifactorial inheritance .
complex .or .polygenic .inheritance
combination .of .environmental .factors .and .mutations .in .multiple .genes,
e.g., .Breast .Cancer . .Mutations .in .Chr .6, .11, .13, .14, .15, .17, .22
Chromosome abnormalities .
Numerical .Disorder, .Trisomy .21,18,13, .Turner, .Klinefelter
Structural .Disorder, .Cri-du-chat .(46,XX .or .XY, .5p-)
Mitochondrial inheritance .
mutations .in .the .non-nuclear .DNA .of .mitochondria
Each .mitochondrion .may .contain .5 .to .10 .circular .pieces .of .DNA
mitochondrial .DNA .is .always .inherited .from .the .maternal .parent.
Leber's .hereditary .optic .atrophy, .mitochondrial .encephalopathy, .lactic .acidosis, .and .stroke-like
.episodes .(MELAS), .myoclonic .epilepsy
