LECTURE 10B: MEIOSIS IN ACTION

first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: prophase: zygotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: prophase: pachytene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: prophase: pachytene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: prophase: diplotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: prophase: diplotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: metaphase I normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: metaphase I normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: anaphase I normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: telophase I normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: telophase I normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: telophase I: first polar body normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: telophase I: first polar body normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

first meiotic division: telophase I: first polar body normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: metaphase II normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: metaphase II normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: anaphase II normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: telophase II normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: telophase II normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

cleavage (mitosis): prophase normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

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

Trisomy 18

Overlapping fist Trisomy 18

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

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

Robertsonian TranslocationReciprocal Translocation vs. Common form of structural rearrangements

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)(q21.3;q25.2)

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 n = 46n = 45 Fusion of two acrocentric chromosome occurs (A) to form a single derivative chromosome (B). 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(13q;14q)

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 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 Deletions WHY??part of being human

Inversion (X)(p11.4q22) associated with Norrie Disease in a 4 generation family. Am J Med Genet 1993;45: Chromosome abnormalities can lead to gene location X-linked

Chromosome abnormalities can lead to gene location

Wolf-Hirshorn syndrome 4p- (Greek warrior helmet) Deletion syndrome

Cri du Chat syndrome 5p- Deletion syndrome

Prader-Willi syndrome Maternal / Paternal

Angelman syndrome – “happy puppet” – del 15q12 Maternal / Paternal

Sex chromosome abnormalities

45,X Turner syndrome

47,XXY Kleinfelter syndrome

Sex Determination 46,XY female SRY on Xp - XX male

Fragile X syndrome

Notice physical the similarities

Fragile X chromosomes vs. DNA Fragile X site

The