HUMAN GENETICS Dr. D.A.R.K. Dayarathna MD (medicine –col), MSc (medical genetics –Ncl - UK)

genetics ppt 01

  • Upload

  • View

  • Download

Embed Size (px)


presentation by- DARK. Dayaratna (consultant physician, MSc in genetics)

Citation preview

Page 1: genetics ppt 01


Dr. D.A.R.K. Dayarathna

MD (medicine –col),

MSc (medical genetics –Ncl - UK)

Page 2: genetics ppt 01


• Human genetics- scientific study of human variation and Heredity

• Medical genetics - study of the hereditary nature of human disease

• Clinical genetics- Care, diagnosis and counseling of patients with congenital malformations or genetic diseases

Page 3: genetics ppt 01

Causes of diseases

• Accidents

• Infections

• Genetic diseases

• Complex traits

Page 4: genetics ppt 01

Genetic diseases

• Inherited diseases

• Diseases due to mutations in somatic cells- cancer

Page 5: genetics ppt 01

Inherited diseases

• Due to genetic mutations- nuclear, Mitochondrial

• Chromosomal abnormalities

• Complex traits, multifactorial disorders

Page 6: genetics ppt 01

Mutations• Deletions- ranging from 1 bp to mega base• Insertions- including duplications• Single base substitution-• Missense mutations- replace one amino

acid with another in the gene product• Nonsense mutations replace one amino

acid codon with a stop codon• Splice site mutations create or destroy

signals for exon/intron splicing• Frame shifts can be produced by

deletions, insertions or splice mutations

Page 7: genetics ppt 01

Mutation- functional change

• Loss of function mutations• Gain of function mutations

Page 8: genetics ppt 01

Loss of function

• Autosomal recessive disorders

Page 9: genetics ppt 01
Page 10: genetics ppt 01

Autosomal dominant

• Dominant negative• Haplo insufficiency

Page 11: genetics ppt 01

Dominant negative mutation

Page 12: genetics ppt 01
Page 13: genetics ppt 01


Page 14: genetics ppt 01
Page 15: genetics ppt 01

Gene structure and protein synthesis

Page 17: genetics ppt 01

GENE expression

Page 18: genetics ppt 01

Down syndrome

Page 19: genetics ppt 01
Page 20: genetics ppt 01

Down syndrome

• Common cause for mental retardation

• Most are due to trisomy 21,nodisjunction

• Elderly mothers are more suseptible

• 2-3% due to translocatin of 21to14

• Screening – triple test

- alpha feto protien


- chorionic

gonadotopihic hormone

- ultra sound scan


Page 21: genetics ppt 01

Turner syndrome

Page 22: genetics ppt 01

Klinefelter syndrome

Page 23: genetics ppt 01

Fragile X syndrome

Page 24: genetics ppt 01

Fragile X syndrome• Inherited cause of

intellectual disability

• Large protruding ears,large testiclesle

• Due to mutation of the fragile X mentel retardation 1 ( FMRI)

• X linked dominent condition with variable expressivity

Page 25: genetics ppt 01

Autosomal dominant inheritance

• Males and females are equally affected• Transmission between all sexes are

observed . Male to male, female to male• Symptoms usually appear later in life• Pleiotrophy- single gene disorder produce

multiple phenotypic effect• Variable expressivity of gene

• Reduced or incomplete penetrance, the

penetrance is expressed as a percentage

Page 26: genetics ppt 01

Autosomal dominant ctd

• Codominance- when both traits are expressed fully in heterozygous state. Ex-AB blood group

• Intermediate inheritance• Ex- sickle cell trait

Page 27: genetics ppt 01

Pedigree symbols

Page 28: genetics ppt 01
Page 29: genetics ppt 01


•Common genetic cause of dwarfism

•Mutation in the fibroblast growth factor receptor


•Cause abnormality of cartilage formation

•Can be detected before birth by prenatal


Page 30: genetics ppt 01

Autosomal dominant polycystic kidney disease

•Inherited systemic disease

• 1 in 400 to 1 in 1000

•Mutation in PKD1 and PKD 2 gene

•Cyst in liver, pancreas, cerebral aneurysm, mitral

valve prolapse.

•Imaging and molecular studies

Page 31: genetics ppt 01

Neurofibramatosis•Skin fibromas

•Neuro fibromas

•Capu lau spot

•Variable clinical manifestation

Page 32: genetics ppt 01

Hereditary spherocytosis

Page 33: genetics ppt 01

Hypertropic obstructive cardiomyopathy

• Presentation

Sudden death

Chest pain on excretion


Page 34: genetics ppt 01

Mafan syndrome

Page 35: genetics ppt 01

Osteogenesis imperfecta

Page 36: genetics ppt 01

Familial hypercholesterolemia

Page 37: genetics ppt 01

Brugada Syndrome

• More in asia

• Cause of sudden death in young

• Can present with atypical chest pain and recurrent palpitation

• Mutation in sodium ion channels

• Cause of death is VF

• Implantable cardioverter defibrillator

Page 38: genetics ppt 01
Page 39: genetics ppt 01

Autosomal recessive inheritance

• Presentation - in early age, usually with severe symptoms

• Affect either sex

• Affected people are usually born to unaffected parents

• Parents are usually asymptomatic carriers

• Increase incidence of parental consanguinity

• After the birth of an effected child, each subsequent child has a 25% of being Affected

Page 40: genetics ppt 01

Autosomal recessecive pedigree

Page 41: genetics ppt 01


Page 42: genetics ppt 01
Page 43: genetics ppt 01


Page 44: genetics ppt 01

White Tiger

Page 45: genetics ppt 01

X linked recessive inheritance

• Affect mainly males• Affected males are usually born to un

affected parents• Mother is normally an asymptomatic

carrier• There is no male to male transmission in

the pedigree

Page 46: genetics ppt 01
Page 47: genetics ppt 01

Color blindness(X-linked)

Page 48: genetics ppt 01
Page 49: genetics ppt 01

Duchenne muscular dystrophy• Common inherited

muscular dystrophy

• Mutation in dystrophin gene

• Symptoms before age of 05

• Progressive muscle weakness

• Pseudo hypertrophy of calf muscles

• Cardiac involvement

Page 50: genetics ppt 01

Lyon hypothesis

• Random inactivation of one X chromosome in early foetal development

Page 51: genetics ppt 01
Page 52: genetics ppt 01

X linked dominant inheritance

• Affect either sex but more female then males

• Female are often more mildly and more variably then males

• No male to male transmission

Page 53: genetics ppt 01
Page 54: genetics ppt 01

Mitochondrial inheritance

• Matrineal inheritance• Variable clinical manifestation due to


Page 55: genetics ppt 01
Page 56: genetics ppt 01
Page 57: genetics ppt 01

Mitochondrial inheritance ctd

Page 58: genetics ppt 01

Mitochondrial disease

• Ragged Red Fibers" - clumps of diseased mitochondria accumulate in the subsarcolemmal region of the muscle fiber and appear as "Ragged Red Fibers" when muscle is stained with modified Gömöri trichrome stain

Page 59: genetics ppt 01

E/M view of diseased mitochondria

Page 60: genetics ppt 01

Mitochondrial myopathies

• Kern sayare syndrome

• Chronic progressive external opthalmoplegia

Page 61: genetics ppt 01

Complex traits

Diabetes mellitus, Hypertension, mental disorders etc

Page 62: genetics ppt 01

Complex traits ctd

• Gene and environment interaction• Population studies• Family studies• Twin studies