Practical 7 07

Practical 7 Numerical chromosomal abnormalities – conclusion

Nondisjunction of sex chromosomes during spermatogenesis – 1 st meiotic division XY XY XY XY XXY XXY X X +X nondisjunction fertilization

Nondisjunction of sex chromosomes during spermatogenesis – 2 nd meiotic division – X chromosome XY Y X XX Y Y XXX X XY XY +X nondisjunction fertilization

Nondisjunction of sex chromosomes during spermatogenesis – 2 nd meiotic division – Y chromosome XY Y X X X YY XX XX XYY X +X nondisjunction fertilization

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

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

Practical 7 Structural chromosomal abnormalities

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. Photo 1 gap breakage triradial quadriradial chromatid breakage chromosomal (double-chromatid) breakage

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

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

Terminal deletion of short arms of the chromosome 5 46,XY,del(5)(p15.2) Simplified finding: 46,XY,del(5p)

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

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

Robertsonic translocation of chromosomes 14 and 21 Down syndrome – translocation form der(14;21)

Robertsonic translocation = robertsonic fusion = centric fusion Translocation of two acrocentric chromosomes, centromeric fusion. derivative chromosome

46,XY,der(14;21)(q10;q10),+21 older description : 46,XY,t(14;21)

For calculation of the risk for further offspring karyotyping of parents is necessary.

Karyotype of the mother balanced robertsonic translocation of chromosomes 14 and 21 Photo – karyotype 5

45,XX,der(14;21)(q10;q10) older description: 45,XX,t(14;21)

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.

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:

Task 5 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 6 – karyotype of the child

Robersonic translocation of two 21 chromosomes Translocation form of the Down syndrome der(21;21)

46,XY,der(21;21)(q10;q10),+21 older description : 46,XY,t(21;21) der(21;21)

Karyotype of the mother balanced robertsonic translocation of two 21 chromosomes Photo (karyotype) 7 der(21;21)

45,XX,der(21;21)(q10;q10) older description: 45,XX,t(21;21) der(21;21)

Risk for further offspring der(21;21) Risk: 100% +21 fertilization der(21;21) nulisomic gamete m. Down monosomy 21 – lethal during early prenatal development

Task 6 A girl with a Turner syndrome features had been examined in the genetic counselling clinic. Describe her karyotype and determine the chromosomal finding.

Isochromosome of long arm of chromosome X 46,X,i(X)(q10) older description: 46,X,iso(Xq)

Origin of isochromosomes i(Xp) i(Xq) Normal separation in anaphase Abnormal division – origin of i s ochromosomes Xp and Xq

Chromosomal abnormalities in Turner syndrome: Numerical aberrations: X m onosomy : 45,X X m onosomy 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)

Origin of ring chromosome reparation deletion of terminal segments ring chromosome r(X)

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

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 .

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.

See you at the end of the summer term!

Practical 7 07

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Practical 7 07