This document defines key genetics terms and concepts including genes, genomes, genotypes, phenotypes, chromosomes, loci, alleles, haploid, diploid, euploid, aneuploid, karyotype, and pedigrees. It discusses DNA, transcription, and translation. Examples of genetic diseases caused by chromosomal abnormalities like Down syndrome, Turner syndrome, and Klinefelter syndrome are provided. Mutations from physical and chemical agents that can cause genetic diseases are described. Common investigations used to study genetic diseases like karyotyping, PCR, DNA sequencing, and microarray analysis are also summarized.

1. GENETICS
Dr. Mahmudul Huque
Endocrinologist
Department of Diabetes & Endocrinology
Holy Family Red Crescent Medical College

2. DNA

3. Cell
To
Protein

4. GENE
Transcription factors bind
here:
• Hormones, Vit D receptors,
HNF(MODY-3)
Regulatory Region
Promoter; RNA
polymerase Binds
Splicing (Marfan’s syndrome )

5. Karyotype

6. Definitions:
• Genetics:
– Genetics is the study of single or few genes
with their phenotypic effect.
• Gene:
– a locatable region of genomic sequence,
corresponding to a unit of inheritance, when
transcribed and translated gives rise to a
complete protein is called a gene. Gene is
associated with regulatory regions,
transcription regions, and or other functional
sequence regions.

7. • Genome:
– All the haploid DNA sequence in a cell is
genome.
• Genomics:
– Study of all the 21,500 genes and their
interactions is called genomics.
Definitions (Contd.) :

8. Definitions:
• Genotype:
– The genotype is the genetic makeup of a cell, an
organism, or an individual usually with reference to a
specific characteristic under consideration.
• Phenotype:
– A phenotype (from Greek phainein, 'to show' + typos,
'type') is the composite of an organism's observable
characteristics or traits
EXAMPLE

9. Definitions:
• Chromosome:
– A chromosome is an organized
structure of DNA, protein, found in
cells.
– It is a single piece of coiled DNA
containing many genes, regulatory
elements and other nucleotide
sequences along with proteins
(histone, non-histone etc).
– Chromosomes also contain DNA-
bound proteins, which serve to
package the DNA and control its
functions.

10. Definitions:
• Locus:
– A locus (plural loci) is the specific location of a gene or
DNA sequence or position on a chromosome.
• Allele:
– An allele is one of a number of alternative forms of the
same gene or same genetic locus.
– Diploid organisms have one copy of each gene (and
therefore one allele) on each chromosome. If both alleles
are the same, they are homozygotes. If the alleles are
different, they are heterozygotes.
– In a heterozygote organism, the allele that determines the
phenotype is Dominant trait, and the dormant trait is the
Recessive trait.

11. Definitions:
• Haploid:
– 1 set of chromosome : 23 X / Y
• Diploid:
– 2 sets of chromosome : 46 XY / XX
• Euploid:
– N x Haploid (23 X/Y)
• Aneuploid:
– (N x Haploid) ± 1 or 2
– (N x Haploid) - 1 =
– (N x Haploid) + 1 =
• Haploid:
– 1 set of chromosome : 23 X / Y
• Diploid:
– 2 sets of chromosome : 46 XY / XX
• Euploid:
– N x Haploid (23 X/Y)
• Aneuploid:
– (N x Haploid) ± 1 or 2
– (N x Haploid) - 1 = Monosomy
– (N x Haploid) + 1 = Trisomy

12. Pedigree Symbols
Male
Proposita

13. Genetic Disease : Molecular Pathophysiology
• Allelic variation in Axon / Intron
– Variation in phenotype & disease susceptibility.
• Mutation: by radiation & chemicals
– Point mutation
– Insertion & Delation
– Duplication of DNA
– Triplet repeat – Huntington’s Disease
– Defect in DNA reapair
• Chromosomal Abnormality:
– Numerical
– Structural
– Micro-delation

14. Mutagens:
• Physical Agents:
– Ionizing radiation
– Ultra-violate ray.
• Chemical Agents:
– Reactive oxygen species (ROS)
– Formaldehyde
– Vinyl chloride
– Alkylating agents.
• Base analogue
• Heavy metals
• Biological agents:
– Transposons, viruses, bacteria
(H. pylori)

15. Cytogenetic Disorders :
• Nearly 7.5% of conceptions contain different
cytogenetic disorders.
• 50% of all are aborted spontaneously.
Mosaicism:
• Two or more population of cells (genotype) in
same individual. Ex: 45X / 47XXX

16. Chromosomal Abnormality
Autosomal
 Down Syndrome (Trisomy 21)
Sex chromosomal
 Klinfelter syndrome
• Classic (47XXY) 85%
• Mosaic (46XY / 47XXY) 15%
 Turner syndrome
• Classic (45X) 57%
• Abnormal X 14%
• Mosaics (45X / 46XX) 29%

17. Chromosomal Abnormality
Structural abnormality:
Chromosomes are constantly broken and repaired
• If repair is less :
– Fanconi’s Anaemia
– Bloom Syndrome
– Ataxia Talengiectasia
• Delation : loss of portion of chromosome
– Williams Syndrome
– Duchenne muscular dystrophy
• Translocation:
– Reciprocal translocation between chromosomes
– Robertsonian Translocation

18. Chromosomal Abnormality (Contd.)
Number abnormality (aneuploidy):
• Trisomy (2n+1)
– Trisomy 21 – Down Syndrome
– Trisomy 18 – Edward’s Syndrome
– Trisomy 13 – Patau’s Syndrome
• Monosomy (2n-1)
– Turner’s syndrome – 45X

19. Down Syndrome (Trisomy 21)

20. Turner’s syndrome (45X)

21. Klinfelter syndrome (47XXY)

22. Consequence of Genetic Variation
• Loss of function
– Polycystic Kidney Disease (Mutation in PKD1 or
PKD2)
• Gain of function
– Marfan’s Syndrome (Mutation in FBN1)
• Polymorphism
– Haemochromatosis
– α1-antitrypsin deficiency

23. • Inherited Via germ Line (Germ Cells)
• There are different types:
– Allelic Heterogenity
– Locus Heterogenity
– De Novo Mutation
Constitutional Genetic Disease

24. Somatic Genetic Disease
• Not Inherited, Post Zygotic Mutation
• May involve in Regulating cell division (proto-
oncogene) and Tumour Suppressor Gene
– Tumour Formation
• May involve Signaling System
– McCune-Albrite Syndrome

25. Common investigation of DNA in
Genetic Disease
• Constructing a family tree (Pedigree analysis)
• Karyotype analysis:
– Chromosome number
– Chromosome structure
• Flurescent in situ hybridization:
– Small delation detection
• PCR (Polymerase Chain Reaction):
– DNA amplification

26. • DNA Sequencing :
– Detects mutation
• Micro array analysis:
– Deteccts DNA loss or gain
• Radiolabelled DNA
• RFLP (Restriction Fragment Length
Polymorphism) & linkage analysis.