disorders common cause of diseases prolonged handicap and death in human 1 newborns have monogenic diseases like CF SCD etc 05 have chr disorders like Down Synd ID: 927549
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Slide1
Slide2HUMAN GENETICS
Genetic
disorders- common cause of diseases, prolonged handicap and death in human.
1% newborns have monogenic diseases like
CF, SCD etc.
0.5% have
chr
. disorders like Down Synd.
1-3% have
multifactorial
disorders like CHD,
spina
bifida.
40% deaths due to genetic disorders & birth
defects.
Slide3HUMAN CELLS
Human genome has 25000
genes (
basic unit).
Human cell
somatic / germ line (
sperm/ovum)
Each somatic cell has 23 pair of chromosomes (diploid No.).
. 22 pairs of
autosomes
. 1 pair of sex
chr
. (
xx/
xy
).
Germ line cell has 23 chromosome (haploid No.)
. 22
autosome
. 1 sex chromosome(X/Y).
Slide4Slide5Slide6CHROMOSOME
Each chromosome has 2 chromatids .
Upper small arm “p” and lower large “q”.
Attached in center “ centromere ”.
Each p / q arm has 350-850 bands.
Each band has specific serial No.
E.g. William Synd. due to deletion at 7q11.23 means disease gene at band 11.23 of
“q” arm
of chromosome 7.
Slide7Slide8Slide9Genotype/phenotype
Genotype:
Genetic constitution of an individual.
Phenotype:
Observed structural , biochemical and
physiological features of an individual.
Slide10MUTATION
Spontaneous change in genetic material
1-Gain function mutation;
over expression / inappropriate expression of
a gene product . Mostly produce AD disorder
e. g.
achondroplasia
.
2-Loss of function mutation;
observed in AR disorders, 50% enzyme activity
in
hetrozygote
- allow normal function e.g. SCD
Slide11FAMILY HISTORY
Most important screening tool to identify pt.’s
risk for development of variety of diseases.
.
Multifactorial
condition:
Diabetes M .
cleft lip and
palat
, neural tube defects.
.
Single gene
disorders:like
SCD, Cystic fibrosis
osteogenesis
Imperfecta
etc.
. Parents, siblings and
offsprings
share 1/2
genetic material & first cousins 1/8 .
Slide12PEDEGREE NOTATION
It provides a graphic presentation of a family’s structure & medical
Hx
.
Arrow represents Information provider(
proband
).
1
st
degree relative (parents, siblings and children)
share ½ genetic information.
1
st
cousins share 1/8 genetic material.
Slide13Slide14ABNORMALITIES OF CHROMOSOME NO.
Euploidy
:
If a cell has No. of
chr
. exact multiple of 23.
n =23
, haploid cell (ovum/sperm)
2n
= 46
, diploid cell (somatic cell)
3n
= 69
, triploid cell (2 sperm+1 ovum, non-
disjunction , viable only in mosaic case).
. paternal origin—
hydatidiform
mole.
. maternal origin—spontaneously abort.
Slide15ANEUPLOIDY
Abnormal cell having no multiple of 23
chr
.
. It
is most common
chr
. abnormality.
. 3-4%
pregnancies, only
mosaic viable.
. Mostly due to non-disjunction.
.
Monosomy
e.g. Turner synd.(45,X0)
.
Trisomy
, most common e.g.21,18,13.
.
Klinefelter
synd.(47,XXY)
Slide16MITOSIS
Somatic cells divide themselves to grow an organ.
4 stages-
. prophase
. metaphase
. anaphase
.
telophase
Duplication of DNA-divide to 2 daughter cells.
Slide17MEIOSIS
In
reproductive/germ
line
cells (sperm
/ ovum
)
In 2 rounds (meiosis
1 & 2
) it completes.
After duplication of DNA ,one germ line cell (diploid No.=46 chromosome)divide into 4
( haploid No.23
chr
.) gametes(ovum/sperm).
Zygote formation (x + y) maintain diploid No.
Slide18Slide19ABNORMAL CHR. STRUCTURE
TRANSLOCATION:
Transfer of genetic material from one to
other chromosome.
Incidence-1:500 in live
borns
.
Inherited from parent /de novo.
usually
phenotypically
normal.
high chances of miscarriage/
chromosomically
abnormal offspring.
Slide20INVERTION
A chromosome breaks at 2 points , broken piece is inverted & joined into same chromosome.
Incidence-1:100 live
borns
.
Carriers are
phenotypically
normal.
High chances of miscarriage/
chromosomically
abnormal offspring .
Slide21Slide22DELETION / DUPLICATION
Deletion:
A piece of chromosome missing.
Usually associated with mental retardation & malformations.
“5p-” (deletion at “p” arm of chromosome No.5
)
Duplication:
Presence of extra
gen.
material from same
chr
.
Slide23INSERTION
A piece of
chr
. broken at 2 points is incorporated
Into a break in an other part of chromosome.
3 break points required.
May occur between 2 or within
same
chr
.
Carrier have high risk of having offspring with deletion or duplication of inserted segment.
Incidence is rare.
Slide24ISOCHROMOSOME
Two copies of same
chr
. arm joined through a single centromere forming mirror image of one another.
Slide25RING CHROMOSOME
Both ends of a chr.
are
deleted and re-joined to
form a ring.
Carrier are normal/nearly normal /may have
mental retardation & multiple congenital
anomalies.
Slide26SEX CHR. ABNORMALITIES
Incidence
- 1:400 in males & 1:650 in females.
Most common
chr
. abnormalities in live
borns
.
Numerical / structural.
Present in all cell / mosaic.
Carrier have few / no physical & developmental problems.
Slide27TURNER SYNDROME
Incidence
- 1:5000 female live
borns
.
Partial / complete absence of 2
nd
X
chr
.
50
%
pt. have(45,X0) and 50% are mosaic.
95-99% of 45,X0 conceptions miscarried.
Phenotype-variable especially in mosaic pt.
Slide28Slide29Turner Syndrome
Slide30Slide31Slide32Slide33Slide34EDWARD
SYNDROME (
Trisomy
18)
Slide35Slide36Slide37Slide38Slide39Slide40POLYPLOIDY
Euploid cells having >diploid No.(2n=46
)
chr
.
. Also called
heteroploid
cells.
. Usually conceptions not viable.
. Mosaic
karyotypically
normal line viable.
Slide41NOONAN SYNDROM
AD
disorder-
60% cause
is
new mutation.
In both male/ female.
Features almost same as in Turner Synd.
Slide42NOONA SYNDROME
Slide43KLINEFELTER SYNDROME
80% are male with an extra X
chr
. (47,XXY).
Commonest cause of
hypogonadism
& infertility.
50% cause is paternal non-disjunction.
Secondary sex characters- delayed.
50% develop gynaecomastia.
Remained unidentified until puberty.
No intellect , show deficit in language.
Slide44Slide45MOSAICISM
Person with 2
>
cell lines from single zygote.
2% in early pregnancy-
chr
. abnormal mosaic.
Except
trisomies
21,18,13, usually non viable.
Mosaicism
may be in some tissues only.
Germ line /reproductive cells
mosaicism
increase risk of recurrence in affected children.