Sims genetics

How many autosomes:?

–22 pair

How many sex chromosomes?

–1 pair

Females:

–46 XX

Males:

–46 XY

Normal human karyotype is

– Diploid.

Sperm/ Eggs are

– Haploid (carry one copy of each

chromosome).

The sex of newborn is determined by

– Sperm

GENETIC ENVIRONMENTAL

Hemophilia

Osteogenesis imperfecta

Phenylketonuria

Galactosaemia

Duchenemuscular dystrophy

Spina bifida

Ischemic heart disease

Ankylosing spondylitis

Scurvy

Trauma

Tuberculosis

Peptic ulcer

Diabetes mellitus

*HEREDITARY:

Transmitted in the germ line; passed from parents to their

offspring.

*FAMILIAL:

Diseases run in families and represent multifactorial

inheritance. Risk for first degree is 5-10% higher.

*CONGENITAL:

Born with; disease present since birth.

BARR BODY[ SEX CHROMATIN ]

Nucleus

Barr body

# of Barr bodies = # of X chromosomes - 1

Davidson Body

LYON HYPOTHESIS:[ 1961, Mary Lyon ]

1. Only one of the X - chromosomes is

genetically active,

2. Other X of either maternal or

paternal origin undergoes

heteropyknosis and is rendered

inactive.

3. Inactivation of either the maternal or

paternal X occurs at random among all

the cells of the blastocyst on or about

the 16th day of embryonic life.

4. Inactivation of the same X

chromosome persists in all the cells

derived from each precursor cell.

LYON HYPOTHESIS:

INCIDENCE:

• 1 in 800 live births [ overall ]

• Maternal age:

•< 20 yrs - 1 in 1550,

•> 45 yrs - 1 in 30

Flat face

Protruding tongue

Occiput tends to be flat

Low bridged nose

Oblique palpabral

fissure

Epicanthic folds

Slanting eyes

Brushfield spots in iris

Epicanthic fold:

Simian crease

40%- Congenital cardiac defects

ASD, VSD, TOF, PDA.

10-20 fold risk to develop Acute leukemia's:

ALL/AML.

CNS:

Mental retardation, IQ -30.

Develop Alzheimer’s disease -

-- at very young age;

Intestine:

Imperforate anus, duodenal stenosis, Hirschsprung’sdisease.

Sterility:

Arrested spermatogenesis.

Life expectancy:

Most common cause of death:

Congenital heart diseases and leukemia.

With normal heart, only 5% of children with

Down syndrome die before age 10.

After age 10, the estimated life expectancy

is 55 years.

Common cause of male hypogonadism

and infertility.

1 in 1000 live male births,

Presence of one or more extra X

chromosome, 47 XXY.

Rarely diagnosed before puberty,

Clinical features:

Eunuchoid body habitus:

– Long legs, tall and thin.

Small, atrophic testes, small penis.

Lack of secondary sexual characteristics,

Deep voice of high pitch.

Gynecomastia, feminine characters.

IQ - low; mental retardation, behavioral

abnormality.

Karyotype of KFS

Turner Syndrome:

Most common sex chromosome abnormality in females,

Monosomy X; the missing chromosome X is usually of paternal origin.

Incidence: 1/8000 . Most die in infancy

Karyotype of Turner Syndrome:

Clinical features of TS:

Edema of dorsum of hand & foot,

Bilateral neck webbing,

Congenital heart diseases, (COA)

Short stature, hyper convex finger nails.

Broad chest & widely spaced nipples,

Multiple Pigmented nevi,

Amenorrhea [ Primary ],

Infertility, streak ovaries.

Low posterior hair line.

Wide carrying angle (cubitus valgus).

Cystic hygroma of neck > webbed neck

Lymphedema

Streak ovaries

True Hermaphrodite:

( ovary + testis )

Pseudo Hermaphrodite:

( Disagreement between

phenotypic and

gonadal sex )

Pseudo hermaphrodite

Female pseudo hermaphrodite:

* Ovaries,

* Male external genitalia,

Male pseudo hermaphrodite:

.. Testes,

.. Female external genitalia;

MENDELIAN

DISORDERS:

[ MUTANT GENES WITH

LARGE EFFECT ]

Genetic diseases:

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Class I Loss of receptor synthesis

Class II Transport inside cell is impaired

Class III Failure of receptors to bind LDL

Class IV Fail to internalize after binding

Class V Internalized bodies are trapped in endosomes

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MUTATION IN ENZYME PROTEIN

PHENYLKETONURIA

GALACTOSEMIA

LYSOSOMAL STORAGE DISEASES

GLYCOGEN STORAGE DISEASES

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DISEASE ENZYME DEFICIENCY

Pompe’s Disease Lysosomal Glucosidase

Tay Sachs disease Hexosaminidase A

Gaucher disease Glucocerebrosidase

Niemann Pick disease Sphingomyelinase

Hurler disease L-Iduronidase

Hunter disease L-Iduronosulphatesulphatase

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