It content elementary, modern and clinical genetics in brief.

1. Elementary
genetics and
clinical
genetics
Momen Ali Khan
MBBS
Mymensingh Medical College

2. GENETICS
Study of gene, heredity and genetic variation in living organism.
CHROMOSOME
A thread-like structure of nucleic acids and protein found in the
nucleus of most living cells, carrying genetic information in the
form of genes.
Types of chromosome
 Metacentric
 Submetacentric
 Acrocentric
 Telocentric

3. GENE (factor or cistrons)
Functional unit of DNA that carry genetic information.
GENOTYPE
It is the inherited genetic constitution of an individual for any
particular character or trait.
PHENOTYPE
Physical appearance of an individual for any particular trait.

4. KARYOTYPE
It is the chromosomal constitution of an individual or cell.
 Normal male: 46XY
 Normal female: 46XX
 Trisomy 21 male: 47XY + 21
 Trisomy 21 female: 47XX + 21

5. PLOIDY
It denotes the number of chromosomal set (n) in cell.
 One set chromosome means 23 chromosome.
 Haploid cell (n) – sperm, ova
 Diploid cell (2n) - normal somatic cell
 Triploid cell (3n), Tetraploid cell (4n) found in chromosomal
abnormalities

7. BARR BODIES
Somatic cell of normal female presents a heterochromatin
planoconvex body beneath the nuclear membrane (inactivated
X chromosomes).

8. DNA
Polymer of deoxy ribonucleotide.
d-ribonucleotide composed of nitrogen base + deoxyribose
sugar + phosphate.
Nitrogen base are of two type. Purine bases – adenine (A),
guanine (G). Pyrimidine bases are thymine (T), cytosine(C).

10. Order of DNA coiling to chromosomes
 Primary of coiling of 2 DNA into double helix molecule.
 Secondary coliling of dna double helix around
nucleosome to make polynucleosome string.
 Tertiary coiling of ploynucleosome string to form
supercoiled chromatin.
 Quaternary supercoiling of chromatin form chromosome.

11. RNA
Polymer of ribonucleotides.
Types
 Ribosomal RNA
 Transfer RNA
 Messenger RNA
Sites
 Ribosome
 Mitochondria
 Endoplasmic reticulum
 Nucleus

13. MUTATION
Permanent change in the DNA base sequences.
Types
 Genomic mutation
 Chromosomal mutation
 Gene mutation
o Point mutation
 Silent mutation
 Missense mutation. Example – sickle cell anemia
 Nonsense mutation. Example - beta thalassemia
o Frame shift mutation

18. RECOMBINANT DNA TECHNOLOGY
 Molecular diagnosis of disease
 Gene therapy
 DNA fingerprinting
 Production of vaccine
Production of commercial and pharmaceutical product

19. Polymerase chain reaction(PCR)
A technique to amplify apiece of DNA outside a living
cell.
Application
 Diagnosis of infectious disease.
 Diagnosis of genetic disease.
 Production of hormone, protein, vaccine.
 Cancer detection.
 Medico legal use for criminal identification.
 Tissue typing for transplantation surgery.
 DNA analysis.
 Prenatal diagnosis of genetic disease.

20. Blot Template analyzed Probe used Restriction enzyme
Southern DNA Nucleic acid Needed
Northern RNA Nucleic acid Not needed
Western
Protein Antibody Not needed
BLOTTING TECHNIQUE
Standard technique used for isolation of specific DNA, RNA, protein.

21. DNA FINGERPRINTING
Application
Person identification
Identification of parentage in disputed paternity.
Assessment of success of bone marrow transplantation by
identifying donor cells.
PRENATAL DIAGNOSIS
Diagnosis of genetic disorder in fetus at mid trimester of
pregnancy.
Sample used
Chorionic villus cells.
Amniotic fluid cells (by amniocentesis)
Umbilical cord blood cells (cordocentesis}
Maternal blood

22. GENE THERAPY
It is the genetic modification of cells to produce therapeutic
effect.
Disease so far treated by gene therapy
Familial hypercholesterolemia.
Duchene muscular dystrophy.
Cystic fibrosis
Hemophilia
Severe combined immunodeficiency

23. Genetic disorders
Chromosomal disorders (cytogenetic disorder)
Mendelian disorders
Multifactorial disorder
Single gene disorder with nonclassic inheritance

24. Chromosomal disorders
Cytogenetic disorders involving autosome
Down syndrome (trisomy 21)
Edward syndrome (trisomy 18)
Patau syndrome (trisomy 13)
Cytogenetic disorder involving sex chromosomes
Klinefelter syndrome (47 XXXY)
Turner syndrome ( monosomy 45XO)
Hermaphorditism and pseudohermaphorditism

25. Mendelian disorders
Autosomal dominant disorders
Autosomal recessive disorders
X linked dominant disorders
X linked recessive disorders

26. AUTOSOMAL DOMINANT DISORDER
STSTEM DISORDER
nervous Huntington disease
Neurofibromatosis
Myotonic dystrophy
Tuberous sclerosis
Urinary Polycystic kidney disease
Gastrointestinal Familial polyposis coli
Hematopoetic Von Willebrand disease
Hereditary spherocytosis
Skeletal Marfan syndrome
Ehlers-Danlos syndrome
Osteogenesis imperfecta
Achondroplasia
Metabolic Familial hypercholesterolemia
Acute intermittent porphyria

27. AUTOSOMAL RECESSIVE DISORDER
SYSTEM DISORDER
Metabolic Cystic fibrosis
Galactosemia
Phenylketonuria
Homocystinuria
Lysosomal storage disease
Glycogen storage disease
Hematopoetic Thalassemias
Sickle cell anaemia
Skeletal Alkaptonuria
Endocrine Congenital adrenal
hyperplasia
Nervous Friedrich ataxia
Spinal muscular dystrophy

28. X LINKED RECESSIVE DISOREDRS
SYSTEM DISORDERS
Musculoskeletal Duchene muscular dystrophy
Blood Hemophilia A and B
Chronic granulomatous disease
Glucose-6-phosphate dehydrogenase
deficiency
Immune Agammaglobulinemia
Wiskott- Aldrich syndrome
Metabolic Diabetes insipidus
Lesch-Nyhan syndrome
Nervous Fragile-X-syndrome
X LINKED DOMINANT DISORDER only example
VITAMIN D RESISTANT RICKETS

29. Karyotype Percentage
Trisomy 21 type : 47, XX, +21 95
Translocation type: 46,XX,der(14,21) (q10,q10), +21 4
Mosaic type : 46, XX/ 47, XX, +21 1
Down syndrome
It is a cytogenetic disorder involving autosome

30. FEATURES
Mental retardation
Epicanthic fold
Flat facial profile
Abundant neck skin
Simian crease
Congenital heart disease
Intestinal stenosis
Umbilical hernia
Hypotonia
Increase gap between first and second toe
Predisposition to leukemia
Children characteristics
Gentle
Shy manner
More easily directed
Like music

31. Investigation:
Karyotyping
Screening procedure
Sensitivity > 60%, Specificity > 95%
First trimester
o Nuchal translucency
o Pregnancy associated plasma protein-A
o hCG
Second trimester
o hCG
o α-fetoprotein
o unconjugated oestriol(uE3

32. KLINEFELTER’S SYNDROME
Male hypogonadism that occurs when there are two or more X
chromosomes and one or more Y chromosome.
Karyotype
Most common 47,XXY
Features
Lower IQ than sibs
Tall stature
Poor muscle tone
Reduced secondary sexual characterstics
Gynaecomastia
Small atrophic testes
Important genetic cause of male infertility.

33. TURNER’S SYNDROME
Complete or partial monosomy of X chromosome.
Karyotype
Classic: 45,X
Features
Short stature
Webbing of neck
Broad chest and widely spaced nipple.
Cubitus valgus
Pigmented nevi
Peripheral lymphedema at birth
Coarctation of aorta
Streak ovaries, infertility, amenoorrhea

34. HERMAPHORDITISM AND
PSEUDOHERMAPHORDITISM
True hermaphorditism
Implies presence of both testicular and ovarian tissue.
Karyotype
 46, XX -70%
 46, XY-10%
 Mosaicism-20%
 Extremely rare condition with variable phenotype and
ambiguous external genitalia.
.

35. Pseudohermaphorditism
Disagreement betwwen the phenotypic and gonadal sex.
Femal pseudohermaphordite has ovaries but male external
genitalia.
 46,XX chromatin+
 Exposure excessive androgen to female fetus.
 Excessive progesterone in threatened abortion
 Maternal tumor
Male pseudohermaphordite has testicular tissue but
female type genitalia
 46, XY. Chromatin –
 External and internal genitalia variable ,testes rudimentary
to normal.
 Inadequate testosterone and MIS
 Genetic defect in enzyme for production of testosterone.