lecture 10b: meiosis in action. first meiotic division: prophase: leptotene normaltrisomy 21...

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: zygotene

normal trisomy 21

chromosome 21

other chromosomes


first meiotic division: prophase: pachytene

normal trisomy 21

chromosome 21

other chromosomes


first meiotic division: prophase: diplotene

normal trisomy 21

chromosome 21

other chromosomes


first meiotic division: metaphase I

normal trisomy 21

chromosome 21

other chromosomes


first meiotic division: anaphase I

normal trisomy 21

chromosome 21

other chromosomes


first meiotic division: telophase I

normal trisomy 21

chromosome 21

other chromosomes


first meiotic division: telophase I: first polar body

normal trisomy 21

chromosome 21

other chromosomes


second meiotic division: metaphase II

normal trisomy 21

chromosome 21

other chromosomes


second meiotic division: anaphase II

normal trisomy 21

chromosome 21

other chromosomes


second meiotic division: telophase II

normal trisomy 21

chromosome 21

other chromosomes


second meiotic division: second polar bodies

normal trisomy 21

chromosome 21

other chromosomes


fertilization

normal trisomy 21

chromosome 21

other chromosomes


cleavage (mitosis): prophase

normal trisomy 21

chromosome 21

other chromosomes


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


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?


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

http://www.discover.com/?id=19846

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

lecture 10b: meiosis in action. first meiotic division: prophase: leptotene normaltrisomy 21...

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