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Whole-genome array-CGH for detection of submicroscopic chromosomal imbalances in children with mental retardation.

Thuresson AC, Bondeson ML, Edeby C, Ellis P, Langford C, Dumanski JP, Annerén G - Cytogenet. Genome Res. (2007)

Bottom Line: Microarray-based comparative genomic hybridization (array-CGH) is considered to be superior for the investigation of chromosomal aberrations in children with MR, and has been demonstrated to improve the diagnostic detection rate of these small chromosomal abnormalities.The yield of identified de novo alterations detected in this study is somewhat less than previously described, and might reflect the importance of which selection criterion of patients to be used before array-CGH analysis is performed.However, array-CGH proved to be a high-quality and reliable tool for genome-wide screening of MR patients of unknown etiology.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. ann-charlotte.thuresson@genpat.uu.se

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Array-CGH profiles of detected chromosomal abnormalities and confirmatory FISH and MLPA analysis. The array-CGH profiles of DNA derived from three cases versus sex matched reference DNA are shown in panels A, C and E. Panels B and F show the corresponding FISH analysis for each patient, and Panel D the corresponding MLPA analysis. The x-axis displays the distance in Mb along the chromosome from the p to the q telomere, and the y-axis the log2 ratios at each locus. The red lines indicate the threshold for a deletion or a duplication (±4DELETESD). (A) Array-CGH profile of a 7-clone deletion at 20q13.12→q13.13 in case 1. (B) Confirmatory FISH analysis of case 1 using BAC clone RP5-1049G16 (red) located in the deletion and control clone RP5-1054C24 (green). (C) Array-CGH profile of an 8-clone duplication at 17p12→p11.2 in case 2. (D) Profile from confirmatory MLPA analysis of case 2, displaying a duplication of six probes (ID 26 through 31) located in the critical region of dup(17)(p11.2p11.2) syndrome. ID 1–25 and 32–42 display chromosomal locations associated with other syndromes. (E) Array-CGH profile of a 4-clone deletion at 4q28.3→q31.21 in case 3. (F) Confirmatory FISH analysis of case 3 using BAC clone RP11-63M2 (red) located in the deletion and control clone RP11-177L7 (green).
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Figure 1: Array-CGH profiles of detected chromosomal abnormalities and confirmatory FISH and MLPA analysis. The array-CGH profiles of DNA derived from three cases versus sex matched reference DNA are shown in panels A, C and E. Panels B and F show the corresponding FISH analysis for each patient, and Panel D the corresponding MLPA analysis. The x-axis displays the distance in Mb along the chromosome from the p to the q telomere, and the y-axis the log2 ratios at each locus. The red lines indicate the threshold for a deletion or a duplication (±4DELETESD). (A) Array-CGH profile of a 7-clone deletion at 20q13.12→q13.13 in case 1. (B) Confirmatory FISH analysis of case 1 using BAC clone RP5-1049G16 (red) located in the deletion and control clone RP5-1054C24 (green). (C) Array-CGH profile of an 8-clone duplication at 17p12→p11.2 in case 2. (D) Profile from confirmatory MLPA analysis of case 2, displaying a duplication of six probes (ID 26 through 31) located in the critical region of dup(17)(p11.2p11.2) syndrome. ID 1–25 and 32–42 display chromosomal locations associated with other syndromes. (E) Array-CGH profile of a 4-clone deletion at 4q28.3→q31.21 in case 3. (F) Confirmatory FISH analysis of case 3 using BAC clone RP11-63M2 (red) located in the deletion and control clone RP11-177L7 (green).

Mentions: As shown in Fig. 1A, an interstitial deletion spanning seven clones, RP5-1049G16 through RP5-1071L10, was detected at 20q13.12→q13.13, which could be verified by FISH using the two different BAC clones, RP5-1049G16 and RP5-1071L10 located at the detected breakpoints (Fig. 1B, and data not shown). This deletion could not be detected in the parents and was considered de novo and consequently of clinical significance. A fraction of this region, covering RP5-1049G16, has been reported in the Database of Genomic Variants (Tuzun et al., 2005; McCarroll et al., 2006; Redon et al., 2006).


Whole-genome array-CGH for detection of submicroscopic chromosomal imbalances in children with mental retardation.

Thuresson AC, Bondeson ML, Edeby C, Ellis P, Langford C, Dumanski JP, Annerén G - Cytogenet. Genome Res. (2007)

Array-CGH profiles of detected chromosomal abnormalities and confirmatory FISH and MLPA analysis. The array-CGH profiles of DNA derived from three cases versus sex matched reference DNA are shown in panels A, C and E. Panels B and F show the corresponding FISH analysis for each patient, and Panel D the corresponding MLPA analysis. The x-axis displays the distance in Mb along the chromosome from the p to the q telomere, and the y-axis the log2 ratios at each locus. The red lines indicate the threshold for a deletion or a duplication (±4DELETESD). (A) Array-CGH profile of a 7-clone deletion at 20q13.12→q13.13 in case 1. (B) Confirmatory FISH analysis of case 1 using BAC clone RP5-1049G16 (red) located in the deletion and control clone RP5-1054C24 (green). (C) Array-CGH profile of an 8-clone duplication at 17p12→p11.2 in case 2. (D) Profile from confirmatory MLPA analysis of case 2, displaying a duplication of six probes (ID 26 through 31) located in the critical region of dup(17)(p11.2p11.2) syndrome. ID 1–25 and 32–42 display chromosomal locations associated with other syndromes. (E) Array-CGH profile of a 4-clone deletion at 4q28.3→q31.21 in case 3. (F) Confirmatory FISH analysis of case 3 using BAC clone RP11-63M2 (red) located in the deletion and control clone RP11-177L7 (green).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC2874679&req=5

Figure 1: Array-CGH profiles of detected chromosomal abnormalities and confirmatory FISH and MLPA analysis. The array-CGH profiles of DNA derived from three cases versus sex matched reference DNA are shown in panels A, C and E. Panels B and F show the corresponding FISH analysis for each patient, and Panel D the corresponding MLPA analysis. The x-axis displays the distance in Mb along the chromosome from the p to the q telomere, and the y-axis the log2 ratios at each locus. The red lines indicate the threshold for a deletion or a duplication (±4DELETESD). (A) Array-CGH profile of a 7-clone deletion at 20q13.12→q13.13 in case 1. (B) Confirmatory FISH analysis of case 1 using BAC clone RP5-1049G16 (red) located in the deletion and control clone RP5-1054C24 (green). (C) Array-CGH profile of an 8-clone duplication at 17p12→p11.2 in case 2. (D) Profile from confirmatory MLPA analysis of case 2, displaying a duplication of six probes (ID 26 through 31) located in the critical region of dup(17)(p11.2p11.2) syndrome. ID 1–25 and 32–42 display chromosomal locations associated with other syndromes. (E) Array-CGH profile of a 4-clone deletion at 4q28.3→q31.21 in case 3. (F) Confirmatory FISH analysis of case 3 using BAC clone RP11-63M2 (red) located in the deletion and control clone RP11-177L7 (green).
Mentions: As shown in Fig. 1A, an interstitial deletion spanning seven clones, RP5-1049G16 through RP5-1071L10, was detected at 20q13.12→q13.13, which could be verified by FISH using the two different BAC clones, RP5-1049G16 and RP5-1071L10 located at the detected breakpoints (Fig. 1B, and data not shown). This deletion could not be detected in the parents and was considered de novo and consequently of clinical significance. A fraction of this region, covering RP5-1049G16, has been reported in the Database of Genomic Variants (Tuzun et al., 2005; McCarroll et al., 2006; Redon et al., 2006).

Bottom Line: Microarray-based comparative genomic hybridization (array-CGH) is considered to be superior for the investigation of chromosomal aberrations in children with MR, and has been demonstrated to improve the diagnostic detection rate of these small chromosomal abnormalities.The yield of identified de novo alterations detected in this study is somewhat less than previously described, and might reflect the importance of which selection criterion of patients to be used before array-CGH analysis is performed.However, array-CGH proved to be a high-quality and reliable tool for genome-wide screening of MR patients of unknown etiology.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden. ann-charlotte.thuresson@genpat.uu.se

Show MeSH
Related in: MedlinePlus