Translocation: Robertsonian t14q21q

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Translocation Robertsonian t(14q21q)

• Jan Otto
• April 5th, 2007
• Nucleic Acids

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Helpful Vocabulary

• Centromere a specialized site within the
  chromosome, serving as the attachment point for
  the mitotic or meiotic spindle
• Dicentric upon translocation, both (two-di)
  centromeres are attached together
• Monocentric upon translocation, the new
  centromere is a fusion of two or the absence of
  one
• Acrocentric the centromere is very near one end
  creating substantially unequal arms
• Metacentric - the centromere is in the center
  creating two similar (equal or nearly equal)
  length arms
• Submetacentric the centromere is slightly off
  center resulting in only slightly unequal length
  arms

www.wikipedia.com
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Additional Helpful Information

• p describes the short (petite) arm of
  acrocentric chromosomes
• q used to describe the long arm of acrocentric
  chromosomes
• t indicates translocation
• SSR - Simple sequence repeats dispersed
  throughout the genome, and form the basis for
  modern tests that verify paternity, identity etc.
  
• Satellite DNA - consists of highly repetitive
  DNA tend to have a relatively high frequency of
  the nucleotides A and T localized at telomeres
  and centromeres
• Alphoid a-satellite located near centromere
  with high order repeat (171) sequences
• Aneuploidy - is a change in the number of
  chromosomes that can lead to a chromosomal
  disorder

www.wikipedia.com
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Even More Helpful Information

• G-banding - (Giemsa) striping of chromosome
• C-banding used to identify centromere
• R-banding Reverse banding - reverse G-band
  staining (GC rich locations)
• Q-banding (Quinacrine) stain shows active bands
  in chromosome
• NOR nucleaolar-organizing region
• NOR Staining silver staining of NOR of
  satellite DNA
• FISH fluorescent in situ hybridization

www.wikipedia.com, http//facstaff.bloomu.edu/chan
sen/Cells20genes20mol/lect10a.ppt333,10,Slide
10
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Dicentric, Monocentric and Acrocentric Examples
Dicentric
Monocentric
Acrocentric Chromosome 14
http//www.pubmedcentral.nih.gov/articlerender.fcg
i?artid1682527
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Translocation
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Translocation
This slide is for ease of printing. Animated
slides dont often print well.
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Translocation

• Nondisjunction
• No predisposition for the translocation random
  often found to increase in frequency with age.
• Mosaicism
• Occurs post-meiosis multiple versions of cells
  some contain translocation and some dont.
• Robertsonian (ROB)
• Translocation associated with parental
  contribution parental carrier (1916).

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Brief Review of Meiosis
http//www.biology.iupui.edu/biocourses/N100H/ch9m
eiosis.html
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Possible Outcomes
http//www.medscape.com/content/2004/00/49/63/4963
93/art-adnc496393.fig3.gif
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Consequences

• Balanced ROB
• Potential for passing it to offspring/non-viable
  fetuses
• Predominate occurrence during oogenesis
• Males may have infertility issues
• At least one complete chromosome present
• Unbalanced ROB
• Aneuploidy, trisomy and/or monosomy
• Sterility, mental retardation, physical
  anomalies, non-viable fetuses, and various birth
  defects

http//www.livingwithtrisomy.org/
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Frequency of Robertsonian Translocation
Combinations

• Translocations occur in 1/1000 births
• 80 are Robertsonian
• t(13q14q) and t(14q21q) most prevalent

ocw.tufts.edu/Content/20/lecturenotes/293242
http//www.scielo.br/img/fbpe/gmb/v25n3/a03tab03.g
if
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Predisposition for TranslocationAcrocentric
http//www.ncbi.nlm.nih.gov/mapview/map_search.cgi
?taxid9606
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Predisposition

• p-arm regions of 14 and 21 are believed
  homologous
• Possible pericentric inversion of the
  a-satellites ? predisposition for translocation
• transposition thought to occur in chromosome 14
• Make it more attractive to chromosomes 13 and
  21 (higher percentage of translocations)
• Long stretches of repeating sequences
• 13, 14, 15, 21, and 22 have similar a-satellite
  regions

Earle et al., 1992
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Chromosome 14
Chromosome 21

http//www.ncbi.nlm.nih.gov/mapview/maps.cgi?taxid
9606chr14
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Translocation

• Complete or partial p-arm deletion on both
  chromosomes
• q-arm possible modification
• New centromere(s)
• submetacentric
• Monocentric or Dicentric

http//www.ncbi.nlm.nih.gov/map
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Identification and Characterization
Q Banding

• Types of staining and testing used (in order of
  use)
• NOR Staining
• C- G- R- Q-banding
• FISH

FISH
Banding
http//biology200.gsu.edu/houghton/862020'06/lect
ure3.html
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Fluorescence In Situ Hybridization(FISH)
www.urovysion.com/FISH_348.asp
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FISH

• Various binding methods
• Fluorescent markers on non-binding side
• Custom design for specific purpose
• Targeting of specific regions based on sequences

learn.genetics.utah.edu/.../williams.cfm
http//www.genome.gov/glossary.cfm?keyfluorescenc
e20in20situ20hybridization20(FISH)
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FISH Flow Chart
http//www.bio.davidson.edu/Courses/Molbio/MolStud
ents/spring2003/Baxter/MolecularTool.html
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Characterization Using FISH

• Lack of rDNA sequences found in normal
  chromosomes, p-arm telomeres
• ROB Translocations
• Various break points (fragile regions)
• Distal alphoid DNA at the centromere
• Proximal to the rDNA and satellite DNA sequences
• Often result in dicentric centromeres
• Stable
• Structurally identical within a family
• Non-identical outside family grouping

Wolf and Schwartz, 1992
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Currently

• Human Genome Mapping
• Targeting of specific subtelomers
• Chromosome specific
• Identification of the genetic information deleted
  in p-arms of the specific acrocentric chromosomes
• FISHing
• Prenatal diagnosis for known carriers
• Follow up testing of abnormal prenatal tests
• Genetic screening
• Dual and Multi-Colored (up to 5) FISH dyes

Cotter, Musci, Norton, 2003, http//biology200.gsu
.edu/houghton/862020'06/lecture3.html
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Summary

• Translocations differ from transpositions
• Translocations occur 3 ways and in 1/1000 live
  births have a variety of outcomes
• Acrocentric chromosomes predisposed to
  translocations
• Breakpoints proximal to the centromere
• q-arm of one inverts and forms new centromere(s)
  with other p-arms deleted
• Stable within family
• FISHing used for prenatal testing for
  Robertsonian translocations

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Sources

• Bandyopadhyay R, Berend SA, Page SL, Choo KH,
  Shaffer LG. Chromosome Res. 2001 9(3)235-42.
• Cheng EY, Naiuai-Cecchini T. Am. J. Obstet.
  Gynecol. 2004 Jun190(6)1781-7
• Choo KH, Vissel B, Brown R, Filby RG, and Earle
  E. Nucleic Acids Research. 1988 Vol. 16, No. 4,
  1273-1284
• Earle E, Shaffer LG, Kalitsis P, McQuillan C,
  Dale S and Choo KH. Am. J. Hum. Genet. 1992
  50717-724
• Wolff DJ and Schwartz S. Am. J. Hum. Genet.
  1992 50174-181
• www.ncbi.nlm.nih.gov. Last accessed 3/12/07
• www.wikipedia.com Last accessed on 3/12/07
• Cotter PD, Musci TJ, and Norton ME.. Am. J. Hum.
  Genet. 2001 Sep 12122(1)1-5
• Gravholt CH, Friedrich U, Caprani M, Jorgensen
  AL. Genomics, 1992 Dec14(4)924-30.
• Choo KH. Mol Biol Med. 1990 Oct 7(5)437-49
• http//biology200.gsu.edu/houghton/
• http//www.bio.davidson.edu/Courses/Molbio/MolStud
  ents/spring2003/Baxter/MolecularTool.html