Download - Practical 7 07
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Practical 7
Numerical chromosomal abnormalities –
conclusion
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Nondisjunction of sex chromosomes during spermatogenesis – 1st meiotic
division
XY
XY
XY XY
XXY XXY X X+X
nondisjunction
fertilization
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Nondisjunction of sex chromosomes during spermatogenesis – 2nd meiotic
division – X chromosome
XY
YX
XX Y Y
XXX X XY XY+X
nondisjunction
fertilization
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Nondisjunction of sex chromosomes during spermatogenesis – 2nd meiotic
division – Y chromosome
XY
YX
X X YY
XX XX XYY X+X
nondisjunction
fertilization
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Barr body
• = sex-chromatin
• Inactivated X chromosome
• Female XX
– 1 Barr body
• Male XY
– no Barr hody
• Klinefelter syndrome XXY
– 1 Barr body
Murray L. Barr
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Task 1: Describe following karyotype according to ISCN1995. How much Barr bodies are present in
somatic cells of this individual?
• 49,XXXXY
• Rare form of
Klinefelter
syndrome
• 3 Barr bodies
Number of Barr bodies = X chromosome number – 1
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Practical 7
Structural chromosomal abnormalities
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Task 2: The photo 1 shows multiple structural abnormalities after irradiation of an individual with
high dosage of X-rays. Describe structural chromosomal aberrations on the photo.
gap
breakage
triradial
quadriradial
chromatid breakage
chromosomal (double-chromatid) breakage
Photo 1
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Origin of structural chromosomal abnormalities
• Incorrect repair of chromosomal
breakages – mainly interchromosomal
rearrangements
• Non-reciprocal crossing-over during
meiosis I. – intrachromosomal
rearrangements – microdeletion
syndromes, X;Y translocation
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Task 3
• A boy (see photo) with severe mental retardation had been cytogenetically examined – see karyotype.
• Describe corresponding chromosomal abnormality and determine the cytogenetic finding.
Karyotype 3
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Terminal deletion of short arms of the chromosome 5
46,XY,del(5)(p15.2)
Simplified finding: 46,XY,del(5p)
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Cat cry syndrome Cri du chat syndrome
• A disorder caused by the loss of part of the short (p) arm from chromosome 5. Also called the cri du chat (or cri-du-chat) syndrome.
• incidence varies between 1 in 20,000 to 1 in 50,000 births. • The frequency of the syndrome among profoundly retarded patients
(with an IQ less than 20) is approximately 1 in 100.
• severe developmental and mental retardation (IQ below 20)
• characteristic constellation of congenital malformations:– microcephaly (small head)
– round face
– hypertelorism (wide-spread eyes)
– micrognathia (small chin)
– epicanthal folds (inner eye folds)
– low-set ears
– hypotonia (poor muscle tone)
– some patients survive into adulthood
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Task 4• A child with the Down
syndrome had been cytogenetically examined. The mother and the father are healthy.
• Describe the chromosomal abnormality in the child and put down the cytogenetic finding.
• Calculate the risk for further offspring of the mother.
Photo – karyotype 4
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Robertsonic translocation of chromosomes 14 and 21
Down syndrome – translocation form
der(14;21)
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Robertsonic translocation
= robertsonic fusion
= centric fusion
Translocation of two acrocentric chromosomes, centromeric fusion.
derivative chromosome
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46,XY,der(14;21)(q10;q10),+21older description: 46,XY,t(14;21)
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For calculation of the risk for further offspring karyotyping of
parents is necessary.
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Karyotype of the mother
balanced robertsonic translocation of chromosomes 14 and 21
Photo – karyotype 5
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45,XX,der(14;21)(q10;q10)older description: 45,XX,t(14;21)
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The mother is carrier of balanced robertsonic translocation of
chromosomes 14 and 21. She is healthy but her offspring has increased risk of the Down
syndrome.
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Risk for further offspring
Normal karyotype
Carrier M. Down Trisomy 14
Monosomy 21
Monosomy 14
Lethal during prenatal development
Theoretical risk 1/3 … 33%
Empiric risk 8 – 10%
Chromosomal constitution of mother carrier:
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Task 5Photo 6 – karyotype of the child
• A child with the Down syndrome had been cytogenetically examined. The mother and the father are healthy.
• Describe the chromosomal abnormality in the child and put down the cytogenetic finding.
• Calculate the risk for further offspring of the mother.
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Robersonic translocation of two 21 chromosomes
Translocation form of the Down syndrome
der(21;21)
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46,XY,der(21;21)(q10;q10),+21
older description: 46,XY,t(21;21)
der(21;21)
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Karyotype of the mother
balanced robertsonic translocation of two 21 chromosomes
Photo (karyotype) 7
der(21;21)
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45,XX,der(21;21)(q10;q10)older description: 45,XX,t(21;21)
der(21;21)
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Risk for further offspring
+21fertilization
der(21;21) nulisomic gamete
der(21;21)
m. Downmonosomy 21 – lethal during early prenatal development
Risk: 100%
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Task 6A girl with a Turner syndrome features had been
examined in the genetic counselling clinic. Describe her karyotype and determine the
chromosomal finding.
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Isochromosome of long arm of chromosome X46,X,i(X)(q10)
older description: 46,X,iso(Xq)
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Origin of isochromosomes
i(Xp)
i(Xq)
Normal separation in anaphase Abnormal division – origin
of isochromosomes Xp and Xq
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Chromosomal abnormalities in Turner syndrome:
• Numerical aberrations:
– X monosomy : 45,X
– X monosomy in mosaic: 45,X/46,XX
• Structural aberrations:
– Isochromosome Xq, isochromosome Xp
– Deletion forms: „46,X,del(Xp)“, „46,Xdel(Xq)“
– Ring chromosomes: 46,X,r(X)
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Origin of ring chromosome
reparationdeletion of terminal
segments
ring chromosome
r(X)
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Task 7
• A boy (see photo) with mental retardation, long narrow face, large ears, a high arched palate, flat feet and overly flexible joints (especially the fingers) had been cytogenetically examined. The karyotype contained abnormality on chromosome X – see partial karyotype.
• Describe X-chromosomal abnormality and determine the cytogenetic finding.
Photo 2 – partial karyotype of chromosome X
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Fragile site on band Xq27.3• 46,Y,fra(Xq27.3)
• Gene responsible for fragile X syndrome is called FMR1
(fragile X mental retardation 1).
• The gene appears in three forms that are defined by the
number of repeats of a pattern of DNA called CGG
repeats:
– Individuals with less than 60 CGG repeats have a normal
gene.
– Individuals with 60 – 200 CGG repeats have a premutation
(they carry an unstable mutation which can expand in
future generations).
– Individuals with over 200 repeats have a full mutation
which causes fragile X syndrome. The full mutation causes
the gene to shut down or methylate a region of the FMR-1
gene.
• Normally, the FMR-1 gene produces an important
protein called FMRP. When the gene is turned off, the
individual does not make fragile X mental retardation
protein (FMRP). The lack of this specific protein causes
fragile X syndrome.
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Fragile X syndrome• the most common inherited cause
of mental impairment.
• The syndrome occurs in approximately 1 in 3600 males.
• the most common cause of inherited mental impairment. This impairment can range from learning disabilities to more severe cognitive or intellectual disabilities.
• the most common known cause of autism or "autistic-like" behaviors.
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See you at the end of the summer term!