LECTURE 10B:MEIOSIS IN ACTION

first meiotic division: prophase: leptotene

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: prophase: leptotene

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: prophase: leptotene

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: prophase: leptotene

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: prophase: leptotene

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: prophase: leptotene

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: prophase: leptotene

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: prophase: leptotene

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: prophase: zygotene

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: prophase: pachytene

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: prophase: pachytene

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: prophase: diplotene

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: prophase: diplotene

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: metaphase I

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: metaphase I

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: anaphase I

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: telophase I

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: telophase I

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: telophase I: first polar body

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: telophase I: first polar body

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

first meiotic division: telophase I: first polar body

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: metaphase II

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: metaphase II

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: anaphase II

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: telophase II

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: telophase II

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: second polar bodies

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: second polar bodies

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: second polar bodies

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: second polar bodies

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: second polar bodies

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: second polar bodies

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: second polar bodies

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: second polar bodies

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: second polar bodies

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

second meiotic division: second polar bodies

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

fertilization

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

fertilization

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

fertilization

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

fertilization

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

fertilization

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

fertilization

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

fertilization

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

fertilization

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

fertilization

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

fertilization

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

fertilization

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

fertilization

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

fertilization

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

fertilization

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

cleavage (mitosis): prophase

normal trisomy 21

chromosome 21

other chromosomes

© 2003 H. NUMABE M.D.

Down Syndromeor

Trisomy 21Karyotype

47,XY,+21

The term“Mongolism” is notappropriate

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 / palateholoprosencephaly

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 Translocation Reciprocal Translocationvs.

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 = 46 n = 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

TranslocationDuring meiosis

Gametes fromCarrier

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 reinsertedif it includes the centromere - pericentricif 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;45:577-580.

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

SRY Sex Region on the Y TSA Three Stooges Appreciation Csy Curly Stimulation Factor, MAC Gadgetry locus FLP Channel Flipping BLZ- 1 Catching and Throwing BLZ- 2 Self- confidence (unlinked to ability) NAV Navigating gene I AD I nability to ask directions GOT- 1 Ability to remember and tell jokes BBQ Barbecuing gene BUD- E Sports Page T- 2 Addiction to death and destruction movies RI F Air Guitar playing DC- 10 Ability to identify aircraft

MOM- 4U Preadolescent fascination with Arachnida/Reptilia P2E Spitting TR Sitting on toilet reading (linked to Sports Page) ME- 2 I nability to express aff ection over the phone HUH? Selective hearing loss FTC Failure to Commit OOPS Total lack of recall for dates

45,X Turner syndrome

47,XXYKleinfelter syndrome

Sex Determination

46,XYfemale

SRY on Xp - XX male

Fragile X syndrome

Fragile X syndrome

Notice physical the similarities

Fragile X chromosomes vs. DNA

Fragile X site

• The