Telomere position effect influences in human terminal deletions Public

Abstract

Copy number variation (CNV) such as deletions and duplications are a well-known cause of intellectual disability and congenital anomalies. In most cases altered expression of the genes that are gained or lost explain the phenotype. However, alternate mechanisms are necessary to further explain other pathogenic CNV. Telomere position effect (TPE) is the silencing of intact genes adjacent to telomeres as a result of heterochromatin spreading from the telomere, which is known in artificially generated truncated chromosomes from yeast to humans. Here eight cell lines with different terminal deletions were studied to understand how gene expression and chromatin environment is changed as a result of the deletion on naturally occurring chromosomes. In a cell line from a patient with a 5.5-megabase deletion of chromosome 4 there was a ~300-kilobase (kb) region extending from the breakpoint that was enriched for heterochromatic modifications associated with the telomere. Analysis of gene expression within and outside this region shows silencing and allele-skewing of a gene that is ~150-kb from the breakpoint in the region of increased heterochromatin, but normal biallelic expression from a gene ~650-kb from the breakpoint, beyond the region of altered chromatin environment. Analysis by ChiP-chip did not reveal this classical TPE near the breakpoint. This demonstrates that a new telomere can have a cis-effect on nearby genomic regions.

Table of Contents

CHAPTER 2: PROJECT

1. HYPOTHESIS...8

2. MATERIALS AND METHODS ...9

3. RESULT...13

FIGURE 1 ...20

FIGURE 2 ...21

FIGURE 3 ...22

FIGURE 4 ..23

FIGURE 5 ..24

FIGURE 6 ...25

TABLE 1 ...26

TABLE 2 ...27

TABLE 3 ...28

TABLE 4 ...29

CHAPTER 3: DISCUSSION ...30

FIGURE 7 ...37

FIGURE 8 ..38

REFERENCES ...39

About this Master's Thesis

Rights statement

• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Laney Graduate School
Department	Biological and Biomedical Sciences
Subfield / Discipline	Genetics and Molecular Biology
Degree	MS
Submission	Master's Thesis
Language	English
Research Field	Biology, Genetics
Mot-clé	position effect chromosome abnormalities
Committee Chair / Thesis Advisor	Rudd, Katie, Emory University Deal, Roger, Emory University
Committee Members	Vertino, Paula M, Emory University Caspary, Tamara, Emory University Moreno, Carlos S, Emory University

Dernière modification

Primary PDF

Thumbnail	Title	Date Uploaded	Actions
	Telomere position effect influences in human terminal deletions ()	2018-08-28 12:57:58 -0400	Press to Select an action Download

Supplemental Files

Thumbnail	Title	Date Uploaded	Actions