The+Genes+Involved+in+OI

What are the genes which cause OI? There are 8 known Genes which cause the various types of OI. Most of these effects are due to mutations in Procollagen type 1 which is essential for fibril formation leading to the abundance of the collagen protein which is used for cartilage and bone development. Below is a table which lists the genes and the pathway which are effected by their mutation or absence. The severity of the disease is varied due to the complete absence of a gene or to their partial absence.

Procollagen is used in cartilage formation. Partial Expression: Moderate bone dysplasia Complete Absence: Lethal in all cases || Procollagen is used in cartilage formation. Partial Expression: Moderate bone dysplasia Complete Absence: Lethal in all cases || Absence increases rate of transit of type 1 procollagen and compromises helical structure. ||
 * **Gene** || **Effect on Pathway** ||
 * **COLIA1 ****5 ** || Involved in forming the triple helix which forms proollagen type 1. ||
 * **COLIA2 ****4 ** || Involved in forming the triple helix which forms proollagen type 1. ||
 * **CRTAP ****2 ** || Absence or lack of Prolyl 3-hydroxylation (P3H1) which fold and stabilize which then contribute to the secretion of procollagen and disrupt the triple helix formation.
 * **<span style="font-family: Arial,sans-serif; font-size: 10pt;">LEPRE1 ****<span style="font-family: Arial,sans-serif; font-size: 7pt;">2 ** || <span style="font-family: Arial,sans-serif; font-size: 10pt;">Absence or lack of Prolyl 3-hydroxylation (P3H1) which fold and stabilize which then contribute to the secretion of procollagen and disrupt the triple helix formation.
 * **<span style="font-family: Arial,sans-serif; font-size: 10pt;">PPIB ****<span style="font-family: Arial,sans-serif; font-size: 7pt;">2 ** || <span style="font-family: Arial,sans-serif; font-size: 10pt;">Codes for protein CyPB which is bound with P3H1 and CRTAP. Causes overmodification of procallagen type 1. ||
 * **<span style="font-family: Arial,sans-serif; font-size: 10pt;">SERPINH1 ****<span style="font-family: Arial,sans-serif; font-size: 7pt;">6 ** || <span style="font-family: Arial,sans-serif; font-size: 10pt;">Found in Dauchshaunds, affects protein HSP47 which acts as a monitor to the triple helix formation in type 1 procollagen in the Endoplasmic Reticulum.
 * **<span style="font-family: Arial,sans-serif; font-size: 10pt;">SERPINF1 ****<span style="font-family: Arial,sans-serif; font-size: 7pt;">6 ** || <span style="font-family: Arial,sans-serif; font-size: 10pt;">Loss of pigment epithelium-derived factor (EPDF) which supports proper bone formation and remodeling. ||
 * **<span style="font-family: Arial,sans-serif; font-size: 10pt;">SP7 ****<span style="font-family: Arial,sans-serif; font-size: 7pt;">6 ** || <span style="font-family: Arial,sans-serif; font-size: 10pt;">Involved in encoding for an osteoblast specific transcription factor used in bone formation ||



Below are Phylogenetic trees which show the relatedness of OI causing genes to other species which may have similar genes. In figure 2, COL1A2 gene was compared to the dog, the house mouse, cattle and grass carp to the human gene. The numbers to the left of the grouped species signify their related with humans most closely related to the grey wolf in this gene followed by the house mouse. In animals like the house mouse which are often used in labs, we could potentially begin to manipulate the gene and potentially synthesize treatment for gene therapy. In figure 3, I have shown the alignment of the protein sequences which was used to create the phylogenetic tree in figure 2. Figure 4 is the phylogenetic tree of the LEPRE1 gene. The species most closely related found was the Rhesus Macaque with a bootstrap of only 73, although this number is within a good range, using this particular species may not be beneficial in experimental gene therapy due to mutations which may differ drastically from the human gene. Both trees used the default settings in creating the trees with a Bootstrap of 500 in the program MEGA.

**>>> Diagnosis & Treatment >>>**


 * What is Osteogenesis Imperfecta? ||= Classification ||= The Genes Involved ||= Diagnosis and Treatment ||= References ||

Research by: Stacey St.Hilaire University of New Hampshire at Manchester Genomics and Bioinformatic