Research Article
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İskelet Displazilerine Özgü Array-CGH Dizaynı ve Uygulaması

Year 2019, Volume: 1 Issue: 1, 26 - 30, 01.11.2019
https://doi.org/10.38175/phnx.634255

Abstract

İskelet displazileri 42 ana gruba ayrılan 436 hastalıktan oluşmaktadır.
Bu hastalıklar yaklaşık 364 genin bir veya birkaçı ile ilişkilendirilmektedir.
Yüksek rezolüsyonlu array-CGH dizaynı, etiyolojisi ve moleküler temelleri iyi
bilinmeyen genetik hastalıklarda, ileri teknolojik araştırmaların yapılmasına
olanak sağlamaktadır. Bu çalışma için iskelet displazilerine özgü yüksek
rezolüsyonlu yeni bir arrayCGH mikroçip tasarlanması amaçlandı. Çalışmaya; Cerrahpaşa
Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı’na başvuran ve iskelet displazisi
tanısı alan, ancak etiyolojisinde bilinen herhangi bir kromozomal anomali,
rutin moleküler tekniklerle tespit edilebilen bir değişim veya metabolik bir
neden bulunamayan 8 hasta dahil edildi. Tüm genom incelemesi için ISCA
tarafından tasarlanan 44K array-CGH prob grubuna ilave olarak iskelet displazilerinde
tanımlanan 226 gen bölgesine özgü, ekzonik ve intronik alanları da kapsayacak
şekilde 14127 adet prob kullanarak yeni bir mikroçip dizayn edildi. Tasarlanan
bu array-CGH slaytlarından elde edilen veriler CytoGenomics programıyla
değerlendirildi. Hazırlanan mikroçiplerle incelenen hastalarda %85 oranında
başarı sağlandı. Analiz edilen 8 hastanın 7’sinde anlamlı kopya sayısı
değişikliği saptandı. Belirlenen bu değişikliklerin ilişkili sendromlar için
aday genler olabileceği, bu tasarımın modifiye şekilleriyle iskelet displazisi
tanı kriterlerinin yeniden belirlenebileceği, yeni alt tiplendirmelere yol
gösterebileceği ve etiyolojisi bilinmeyen displazilerin moleküler temellerinin
açıklanmasına imkan sağlayabileceği düşünülmektedir.

Supporting Institution

İstanbul Üniversitesi-Cerrahpaşa Bilimsel Araştırma Projeleri Koordinatörlüğü

Project Number

15497

Thanks

Bu projeye desteğinden dolayı İstanbul Üniversitesi-Cerrahpaşa Bilimsel Araştırma Projeleri Koordinatörlüğü'ne teşekkür ederiz.

References

  • 1. Urist M.R., Fundamental and Clinical Bone Physiology, Philadephia: J.B. Lippincott, 1980.
  • 2. Rasmussen S.A., Bieber F.R., et al., Epidemiology of osteochondrodysplasias: changing trends due to advances in prenatal diagnosis. Am J Med Genet. 1996; 61: 49–58.
  • 3. Doray B., Favre R., et al. Prenatal sonographic diagnosis of skeletal dysplasia: A report of 47 cases. Ann Genet. 2000; 43: 163–169.
  • 4. K. A. Geister and S. A. Camper, “Advances in skeletal dysplasia genetics,” Annual Review of Genomics and Human Genetics 2015; vol. 16, pp. 199–227.
  • 5. Savarirayan R., Best Practice & Research Clinical Endocrinology and Metabolism, 2002; 16 (3): 547–560.
  • 6. Lupski J.R., Stankiewicz P., Genomic Disorders, The Genomic Basis of Disease. Humana Press, 2006; Part 27: 389-400.
  • 7. Jao-Shwann L., Shimojima K., Yamamoto T., Application of Array-based Comparative Genome Hybridization in Children with Developmental Delay or Mental Retardation. Pediatr Neonatol., 2008; 49 (6): 213−217.
  • 8. Sung Yoon Cho, Dong-Kyu Jin. Guidelines for genetic skeletal dysplasias for pediatricians. Ann Pediatr Endocrinol Metab 2015;20:187-191.
  • 9. Francomano C.A., Achondroplasia. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-1998 Oct 12 [updated 2006 Jan 09].
  • 10. Kannu P., Oei P., Slater H.R., Khammy O., Aftimos S., Epiphyseal dysplasia and other skeletal anomalies in a patient with the 6p25 microdeletion syndrome. Am J Med Genet Part A 2006; 140A: 1955–1959.
  • 11. Stevenson R.E., Hall J.G., Skeletal Dysplasia. In: Human Malformations and Related Anomalies., 2nd Eds, Chapter 22, 2006; 997-1020.
  • 12. El-Gharbawy A.H., Peeden J.N., Lachman R.S., Graham J.M., Moore S.R., Rimoin D.L., Severe cleidocranial dysplasia and hypophosphatasia in a child with microdeletion of the C-terminal region of RUNX2. Am J Med Genet A. 2010 Jan; 152A (1): 169-74.

Spesific Array-CGH Design and Application in Skeletal Dysplasia

Year 2019, Volume: 1 Issue: 1, 26 - 30, 01.11.2019
https://doi.org/10.38175/phnx.634255

Abstract

Skeletal dysplasia (SD) and associated disorders
classified 42 groups and 436 defined diseases. Totally 364 genes are associated
with SD. The design of high-resolution array-CGH allows research to be done
with advanced technology in the genetic diseases that still unknown etiology
and molecular basis.

The aim of this study was to design a new
high-resolution arrayCGH microchip for skeletal dysplasias.

To work; Eight patients who were admitted to
Cerrahpaşa Medical Faculty, Medical Genetics Department, and diagnosed as
skeletal dysplasia but had no known chromosomal abnormalities, any change that
can be detected by routine molecular techniques or no metabolic cause were
included.







We designed a
microarray slight containing 14127 probes for the intronic and exonic regions
of the 226 SD genes and also the 44K Array-CGH probe group that is standardized
by ISCA. Data obtained from these designed array-CGH slides were evaluated with
the CytoGenomics program. The investigation by this method achieved 85% success
in patients. We detected copy number changes in 7 out of 8 patients. The
detected changes have the possibility of being candidate genes for related
syndromes. We think that the designed microarray slight will be useful for
re-identifying the criteria of SD and new subgroups and also describing the
candidate genes of SD with unknown etiology.

Project Number

15497

References

  • 1. Urist M.R., Fundamental and Clinical Bone Physiology, Philadephia: J.B. Lippincott, 1980.
  • 2. Rasmussen S.A., Bieber F.R., et al., Epidemiology of osteochondrodysplasias: changing trends due to advances in prenatal diagnosis. Am J Med Genet. 1996; 61: 49–58.
  • 3. Doray B., Favre R., et al. Prenatal sonographic diagnosis of skeletal dysplasia: A report of 47 cases. Ann Genet. 2000; 43: 163–169.
  • 4. K. A. Geister and S. A. Camper, “Advances in skeletal dysplasia genetics,” Annual Review of Genomics and Human Genetics 2015; vol. 16, pp. 199–227.
  • 5. Savarirayan R., Best Practice & Research Clinical Endocrinology and Metabolism, 2002; 16 (3): 547–560.
  • 6. Lupski J.R., Stankiewicz P., Genomic Disorders, The Genomic Basis of Disease. Humana Press, 2006; Part 27: 389-400.
  • 7. Jao-Shwann L., Shimojima K., Yamamoto T., Application of Array-based Comparative Genome Hybridization in Children with Developmental Delay or Mental Retardation. Pediatr Neonatol., 2008; 49 (6): 213−217.
  • 8. Sung Yoon Cho, Dong-Kyu Jin. Guidelines for genetic skeletal dysplasias for pediatricians. Ann Pediatr Endocrinol Metab 2015;20:187-191.
  • 9. Francomano C.A., Achondroplasia. In: Pagon RA, Bird TD, Dolan CR, Stephens K, editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-1998 Oct 12 [updated 2006 Jan 09].
  • 10. Kannu P., Oei P., Slater H.R., Khammy O., Aftimos S., Epiphyseal dysplasia and other skeletal anomalies in a patient with the 6p25 microdeletion syndrome. Am J Med Genet Part A 2006; 140A: 1955–1959.
  • 11. Stevenson R.E., Hall J.G., Skeletal Dysplasia. In: Human Malformations and Related Anomalies., 2nd Eds, Chapter 22, 2006; 997-1020.
  • 12. El-Gharbawy A.H., Peeden J.N., Lachman R.S., Graham J.M., Moore S.R., Rimoin D.L., Severe cleidocranial dysplasia and hypophosphatasia in a child with microdeletion of the C-terminal region of RUNX2. Am J Med Genet A. 2010 Jan; 152A (1): 169-74.
There are 12 citations in total.

Details

Primary Language Turkish
Subjects Genetics
Journal Section Research Articles
Authors

Hatip Aydın

Aysel Kalaycı Yiğin

Filiz Özdemir This is me

Mehmet Seven This is me

Project Number 15497
Publication Date November 1, 2019
Submission Date October 17, 2019
Acceptance Date October 24, 2019
Published in Issue Year 2019 Volume: 1 Issue: 1

Cite

Vancouver Aydın H, Kalaycı Yiğin A, Özdemir F, Seven M. İskelet Displazilerine Özgü Array-CGH Dizaynı ve Uygulaması. Phnx Med J. 2019;1(1):26-30.

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