Chromosomal abnormalities
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Transcript of Chromosomal abnormalities
CHROMOSOMAL ABNORMALITIES
PRESENTED BY:DR. BISWAJEETA SAHA(PGT,1ST YR),MODERATOR-DR.A.K.ADHYA(ASST. PROF),DEPT OF PATHOLOGY,KIMS,BBSR
NORMAL KARYOTYPE Karyotype: a picture of the chromosomes from a single cell.
International system for
human cytogenetic
nomenclature.
eg- Xp21.2
Eg-47,XY,+21
NUMERICAL ABNORMALITIES
Euploid-any exact multiple of haploid
Aneuploidy-chromosome compliment that is not an exact
mutiple of 23
Nondisjunction
Anaphase lag
Mosaicism-mitotic error in early development give rise to 2
/more population of cells with different chromosomal
complement in some individual EG-45X/47XXX mosaic
Deletions-loss of a portion of chromosome
STRUCTURAL ABNORMALITIES
Eg-46,XY,del(16)(p11.2p13.1)
RING CHROMOSOME
Eg-46,XY,r(16)
Insertion
Inversion-2 breaks,turns upside down and re-attaches
Eg-inv(9)(p11q12)
Isochromosome-one arm is lost,other arm is reduplicated
Translocation-one segment transferred to another.
Eg-46,XY,t(2:5)(p12;q14)
CLINICAL ABNORMALITIES
SPONTANEOUS ABORTIONS
1 in 200 live born children is chromosomally abnormal
95% of chromosomally abnormal conceptus are aborted
spontaneously
Abortion mostly occurs in 1st trimester
DOWN SYNDROME
Incidence-1 in 700
95% have trisomy 21,chromosome no 47
1% cases are mosaics.-mitotic nondisjunction
4% cases-extra chromosomal material derives from presence of
robertsonian translocationof long arm of chromosome 21 to
acrocentric chromosome.
10 to 20 fold increased risk of deveoping leukemia
CHROMOSOME 22q11.2 DELETION SYNDROME
Small deletion of band q11.2 on long arm of chromosome 22. 1 in 4000 births Congenital heart defects ,palatal abnormalities, facial
dysmorphism, developmental delay,T-cell immunodeficiency and hypocalcemia
High risk for schizophrenia and bipolar disorder
TRISOMY 18
Incidence 1/8000
Overlaps with trisomy 13
Sever Mental retardation
>90% dead in 1st year
Small face with prominant occiput
Small sternum and pelvis
Flexion deformity of the finger
VSD and horseshoe kidney
TRISOMY 13(PATAU SYNDROME)
Severe developmetal retardation
Incidence 1/20000
90% dead in the 1st year
Midline brain defect
Malformed ear
Micropthalmos and coloboma
Scalp defect
CYTOGENETIC DISORDERS AFFECTING SEX CHROMOSOME
More common than autosomal aberrations.
Lyon hypothesis
TURNER SYNDROME Complete or partial monosomy of X chromosome Hypogonadism in phenotypic females 1 in 2000 live born females 57% missing an entire X chromosome-45,X karyotype 14% have structural abnormalities of X chromosome 29% are mosaics Structural abnormalities are- Deletion of small arm-isochromosome of long arm-46,X,i(X)(q10) Deletion of portion of both long and short arms-ring chromosome-46,X,r,(X) Deletion of portion of short or long arm-46X,del(Xq) Mosaic patterns- 45,X/46,XX 45,X/46,XY 45,X/47XXX 45,X/46,X,i(X),(q10)
Female, short stature, primary amenorrhea, sterility, spares
hair and underdeveloped breast
Neonatal: wide spaced nipple, lymphedema , shield chest,
KLINEFELTER SYNDROME
Male hypogonadism occur when there are 2 /more X
chromosome and one /more Y chromosome.
1 in 660 live male births
Eunuchoid body habitus,abnormally long legs,small atrpohic
testis,lack of secondary male characteristics
Increased incidence of type 2 diabetes,metabolic syndrome
Higher risk of breast cancer,extragonadal germ cell tumor and
autoimmune diseases
47,XXY-90% cases
15% cases are mosaics
HERMAPHRODITISM GENETIC SEX
PHENOTYPIC SEX
PSEUDOHERMAPHRODITISM
TRUE HERMAPHRODITISM
FEMALE PSEUDOHERMAPHRODITISM-excessive and
innapropriate exposure to androgenic steroids during early
gestation
MALE PSEUDOHERMAPHRODITISM-extremely
heterogenous.most common –defective virilization of male
embryo(complete androgen insensitivity syndrome)
KARYOTYPING
3 main methods to identify chromosomes
G BANDING-------giemsa
Q BANDING-------quinacrine
R BANDING-------reverse
SUBCLASSIFICATIONS OF BANDING METHODS ISCN 1985
3 letter code to describe banding techniques.
Ist letter---type of banding
2nd letter—general technique
3rd letter—the stain
Eg-QFQ------Q band by flourescence using quinacrine
G BANDING
System of dark and light bands throughout the euchromatin
part of chromosome
Staining technique where chromosomes are treated with
trypsin then with giemsa stain
Needs metaphase
Culture cells until sufficient mitotic activity
Add colchicine to arrest in metaphase
TERMS AND DEFINITIONS OF VARIOUS ABERRATIONS OF CHROMOSOMES
Ring( r)
Dicentric(d) Hyperdiploid (h)
Chromosome gap (sg) Chromatid
deletion (td)
Fragment (f) Acentric fragment
(af)
Translocation (t) Triradial (tr)
Quadriradial (qr)
Complex rearrangement (cr)
Polyploid (pp) or endoreduplication
FLOURESCENT IN SITU HYBRIDISATION(FISH)
Fluorescence in situ hybridization (FISH) uses fluorescent
molecules to “paint” genes or chromosomes.
This technique is for gene mapping, identification of
chromosomal abnormalities
FISH involves the use of short sequences of single-stranded
DNA (probes) which are labeled with fluorescent tags, to
hybridize, or bind, to the complementary DNA to see the
location of those sequences of DNA under the fluorescent
microscope.
metaphase FISH interphase FISH
ADVANTAGES OF FISH
Rapid
High efficiency of hybridization and detection
Lots of cells can be analyzed
Cells do not have to be replicating
SPECTRAL KARYOTYPING
Chromosomal and subchromosomal painting probes that make use of sorted or microdissected chromosomes
Mixtures of fluorophores used to separately label chromosome-
specific probes
These are mixed and hybridized en masse
Interpreted via spectral interferometer
Tremendously useful in detecting insertions and translocations,
especially in cancers.
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