LECTURE 10 B MEIOSIS IN ACTION first meiotic

LECTURE 10 B: MEIOSIS IN ACTION

first meiotic division: prophase: leptotene chromosome 21 other chromosomes normal trisomy 21 © 2003

first meiotic division: prophase: zygotene chromosome 21 other chromosomes normal trisomy 21 © 2003

first meiotic division: prophase: pachytene chromosome 21 other chromosomes normal trisomy 21 © 2003

first meiotic division: prophase: diplotene chromosome 21 other chromosomes normal trisomy 21 © 2003

first meiotic division: metaphase I chromosome 21 other chromosomes normal trisomy 21 © 2003

first meiotic division: anaphase I chromosome 21 other chromosomes normal trisomy 21 © 2003

first meiotic division: telophase I chromosome 21 other chromosomes normal trisomy 21 © 2003

first meiotic division: telophase I: first polar body chromosome 21 other chromosomes normal trisomy

second meiotic division: metaphase II chromosome 21 other chromosomes normal trisomy 21 © 2003

second meiotic division: anaphase II chromosome 21 other chromosomes normal trisomy 21 © 2003

second meiotic division: telophase II chromosome 21 other chromosomes normal trisomy 21 © 2003

second meiotic division: second polar bodies chromosome 21 other chromosomes normal trisomy 21 ©

fertilization chromosome 21 other chromosomes normal trisomy 21 © 2003 H. NUMABE M. D.

cleavage (mitosis): prophase chromosome 21 other chromosomes normal trisomy 21 © 2003 H. NUMABE

Down Syndrome or Trisomy 21 Karyotype 47, XY, +21 The term “Mongolism” is not appropriate

Robertsonian Translocations Other chromosomal forms of Down syndrome - ? inheritance Can result in Down syndrome

Trisomy 13

Polydactyl of Trisomy 13

Trisomy 13 showing cleft lip/palate Trisomy 13 at age 7 yrs.

Trisomy 18

Trisomy 18 Overlapping fist

Other syndromes with physical finding also found in +13 and +18 Cleft lip / palate cyclopsia Cleft lip / palate & holoprosencephaly

When good chromosomes go bad Chromosomal Rearrangements

Chromosome Abnormalities: Structural rearrangements • Chromosome breakage with subsequent reunion in a different configuration – Balanced • no loss or gain of genetic information • position change • no phenotype consequences (except when there is a position effect gene disruption) • reproductive consequences • Unbalanced – loss or gain or chromosome material – abnormal phenotype association

Common form of structural rearrangements Robertsonian Translocation vs. Reciprocal Translocation

Reciprocal Translocation • Balanced translocation results in a position effect only i. e. the exchange of chromosome material between 2 chromosomes • no loss or gain of genetic information, usually no phenotype effect (unless there is a position effect resulting in gene disruption)

Examples of Balanced Structural Rearrangement

Reciprocal Translocations: Points to consider • Look at the karyotype following this slide: – What is the modal chromosome number? – Is there a rearrangement present? – How many derivative chromosomes do you see? – Is this a balanced karyotype and if so, why?

Reciprocal Translocation 46, XX, t(2; 17)(q 21. 3; q 25. 2)

Reciprocal Translocations: Points to consider • Referring to the previous slide: – What is the modal chromosome number? 46 – Is there a rearrangement present? Yes, a reciprocal translocation. – How many derivative chromosomes do you see? Two. – Is this a balanced karyotype and if so, why? There is no apparent cytogenetic loss or gain of chromosome material, just a repositioning effect.

Robertsonian Translocation • Joining of the long arm of two acrocentric chromosomes to form a single derivative chromosome • loss of p arm material without phenotype effect • modal chromosome number 45 in balanced carriers

Robertsonian Translocation Fusion of two acrocentric chromosome occurs (A) to form a single derivative chromosome (B). n = 46 n = 45 With a balanced Robertsonian translocation, the modal number is reduced from 46 to 45 chromosomes.

Robertsonian Translocation: Points to consider • Look at the karyotype following this slide: – – – What is the modal chromosome number? Is there a rearrangement present? How many derivative chromosomes do you see? Is this a balanced karyotype and if so, why? What material has been lost with this rearrangement, if any?

Robertsonian Translocation 45, XX, der(13 q; 14 q)

Robertsonian Translocation: Points to consider (1) • Referring to the previous slide: – What is the modal chromosome number? 45 – Is there a rearrangement present? Yes, two acrocentric chromosomes have joined at or near the centromere. – How many derivative chromosomes do you see? One, the acrocentric long arms have joined to form a single derivative chromosome. – Is this a balanced karyotype and if so, why? Yes, There is no loss of clinically relevant euchromatin with the formation of a single derivative chromosome.

Robertsonian Translocation: Points to consider (2) • What material has been lost with this rearrangement, if any? The acrocentric p arms of chromosomes 13 and 14 have been lost with this rearrangement. Since the p arms contain ribosomal genes that are found on the short arms of other acrocentric chromosomes, there is no phenotype effect.

Reciprocal vs Robertsonian: • Reciprocal -> 2 derivative chromosomes, 46 chromosomes total • Robertsonian -> 1 derivative chromosome • 45 = balanced • 46 = unbalanced Either may or may not be inherited*

Consequences Of Structural Rearrangements • Balanced carriers · phenotypic risks - low · reproductive risks - > background • increased risk of miscarriage • increased risk of offspring with – mental retardation – congenital anomalies • WHY?

Anatomy of a Translocation During meiosis Gametes from Carrier Gametes from Normal partner Outcome Balanced Normal trisomy & monosomy

Structural Aberrations Balanced rearrangements No visible loss or gain of genetic material: Inversions ( peri- and paracentric) a piece of chromosome flipped around and reinserted if it includes the centromere - pericentric if it excludes the centromere - paracentric These have slightly different genetic consequences as a result of meiotic pairing Can result in abnormal pregnancies and SAB May or may not be inherited*

Other forms of chromosome abnormalities • deletions • duplications • insertions • rings • isochromosomes WHY? ? Deletions part of being human

Inversion (X)(p 11. 4 q 22) associated with Norrie Disease in a 4 generation family. Am J Med Genet 1993; 45: 577 -580. Chromosome abnormalities can lead to gene location X-linked