13q14.3

Chromosomes, intricate structures within the nuclei of our cells, contain the blueprint of life—DNA.  Each chromosome carries genes that encode instructions for building and maintaining our bodies, influencing everything from eye color to enzyme production. 

Chromosome testing helps unravel the complexities of genetic information, enabling clinicians and researchers to diagnose and understand a wide range of genetic conditions. 

As the carriers of genetic material, chromosomes play a pivotal role in heredity and disease susceptibility. The proper function of genes—units of heredity composed of DNA—ensures normal development and bodily functions. 

However, mutations occurring by alteration, deletion, or duplication of DNA segments have consequences ranging from benign to life-threatening. 

Deletion or mutation of 13q14.3, the most common genetic abnormality in chronic lymphocytic leukemia (CLL), is linked to a favorable prognosis and involves key tumor suppressor microRNAs, miR-15a and miR-16-1.  [6.]

What is 13q14.3?

13q14.3 denotes a specific chromosomal region located on the long arm (q arm) of chromosome 13. Within this region lies a cluster of genes that play vital roles in various cellular processes and physiological functions. 

13q14.3 Definition and Chromosomal Location

Positioned on the long arm of chromosome 13, the 13q14.3 region encompasses a stretch of DNA with distinct genetic characteristics and functional significance.  

Deletion or mutation of chromosome 13q14.3, the most common cytogenetic abnormality in chronic lymphocytic leukemia (CLL), leads to the loss of tumor-suppressing microRNAs, disrupting apoptosis and contributing to CLL progression. This deletion is associated with a favorable prognosis and has significantly influenced therapeutic strategies and clinical outcomes in CLL.  [3.] 

Candidate genes on chromosome 13q14.3 that may be involved in altered function in CLL include:

• DLEU2 (Deleted in Lymphocytic Leukemia 2)

• MIR15A (microRNA 15A)

• MIR16-1 (microRNA 16-1)

• RB1 (Retinoblastoma 1)

Genes Located within 13q14.3 and Their Functions

DLEU2 Gene  [2.] 

The DLEU2 gene is responsible for creating microRNAs and long non-coding RNAs that do not code for proteins but can regulate other genes. In cases of leukemia, this part of the genome is often missing or turned off, suggesting it plays a role in controlling how fast cells grow and multiply. 

Normally, DLEU2 helps prevent excessive cell growth. Interestingly, another type of RNA made by this gene appears to encourage cell growth by interacting with specific proteins involved in the cell cycle, such as angiotensin I converting enzyme 2 and cyclin D1.

MIR15A Gene  [4.]

The MIR15A gene produces microRNAs (miRNAs), which are short, non-coding RNAs crucial for controlling gene expression in complex organisms.  These miRNAs work by influencing the stability and translation of messenger RNAs (mRNAs). 

Initially, miRNAs start as longer primary transcripts that may or may not code for proteins.  These transcripts are processed in the nucleus by Drosha, an enzyme that trims them into a precursor form. This precursor is then cut by Dicer, another enzyme in the cytoplasm, to produce the mature miRNA. 

This mature miRNA joins a complex called RNA-induced silencing complex (RISC), which helps it bind to target mRNAs.  The binding usually leads to reduced production of proteins from these mRNAs, either by blocking their translation or by causing the mRNAs to degrade.

MIR16-1 Gene  [5.] 

The MIR16-1 gene produces microRNAs (miRNAs), small non-coding RNAs that regulate gene expression after transcription.  These miRNAs impact how messenger RNAs (mRNAs) are both stabilized and translated into proteins. 

MIR16-1 starts as a primary transcript made by RNA polymerase II, which is processed by the Drosha enzyme into a precursor miRNA. This precursor is then further refined by Dicer, another enzyme, to form the mature miRNA. 

This mature miRNA becomes part of a complex known as the RNA-induced silencing complex (RISC).  In the RISC, the miRNA helps find and bind to complementary sequences in mRNAs, typically leading to reduced protein production from these mRNAs either by preventing their translation or by breaking them down.

RB1 Gene  [1.] 

The RB1 gene is crucial for preventing the development of cancers, including the childhood eye cancer retinoblastoma. 

Discovered over 25 years ago, RB1's role extends beyond cancer prevention into essential aspects of normal development. The protein it encodes, pRb, helps control the cell cycle, which is vital for regulating cell growth and ensuring proper cell function. 

Mutations or deactivation of the RB1 gene can disrupt cell cycle control and lead to uncontrolled cell growth, which is a hallmark of cancer.  

Pioneering studies on RB1 have not only enhanced our understanding of cancer mechanisms but also guided the development of new cancer therapies.  By regulating protein complexes on DNA in response to cellular signals, pRb ensures cells reproduce correctly and maintain healthy growth, which is fundamental in both cancer prevention and normal developmental processes.

13q14.3 in Health and Disease

Normal Physiological Roles

Genes located within the 13q14.3 region play integral roles in maintaining normal physiological functions. These genes may participate in processes such as cell cycle regulation, apoptosis, and DNA repair, as well as regulation of gene expression.  

Chromosome 13q14.3 Deletion and Chronic Lymphocytic Leukemia (CLL) Implications in Various Health Conditions

Deletion of chromosome 13q14.3 is the most frequent genetic change in chronic lymphocytic leukemia (CLL), generally associated with a better outlook for the disease. 

This genetic alteration leads to lower levels of certain microRNAs, miR-15a and miR-16-1, which play roles in controlling cell death and growth.  

Identifying this deletion helps predict the course of CLL, with patients showing a lower expression of these microRNAs typically having a milder form of the disease. 

Advanced techniques, such as real-time PCR, are effective in detecting these deletions and can serve as tools for assessing patient prognosis, complementing more traditional methods like FISH (fluorescence in situ hybridization). This offers a clearer understanding of each patient’s condition and helps tailor more effective treatments.

Genetic testing can be done in many ways to identify individuals with specific chromosomal or SNP abnormalities.  Testing for genetic alterations in the form of SNPs is increasingly available and can shed light on an individual’s potential for health and disease.  

What is a SNP?

A SNP, or single nucleotide polymorphism, refers to a variation at a single position in a gene along its DNA sequence.  A gene encodes a protein, so an alteration in that gene programs the production of an altered protein.  

As a type of protein with great functionality in human health, alterations in genes for enzymes may confer a difference in function of that enzyme.  The function of that enzyme may be increased or decreased, depending on the altered protein produced.  

SNPs are the most common type of genetic variation in humans and can occur throughout the genome, influencing traits, susceptibility to diseases, and response to medications.

The completion of the Human Genome Project has significantly expanded opportunities for genetic testing by providing a comprehensive map of the human genome that facilitates the identification of genetic variations associated with various health conditions, including identifying SNPs that may cause alterations in protein structure and function.  

Genetic testing for SNPs enables the identification of alterations in genes, shedding light on their implications in health and disease susceptibility.

Laboratory Testing for 13q14.3

Laboratory testing for 13q14.3 abnormalities plays a crucial role in diagnosing genetic disorders and assessing disease risk.  There are many methods used for laboratory testing of 13q14.3.

Overview of Testing Methods

Genetic testing involves various methodologies to analyze DNA and chromosomes for medical and research purposes. Here are the primary types:

Polymerase Chain Reaction (PCR): this technique amplifies small DNA samples to detect or measure specific genes or regions. It's widely used for identifying genetic variants associated with diseases.

DNA Sequencing:

Sanger Sequencing: once the standard for clinical DNA sequencing, this method involves marking DNA nucleotides with fluorescent dyes to read sequences. It's precise but limited to short DNA sections and one sample at a time.

Next-Generation Sequencing (NGS): this includes whole exome and whole genome sequencing, capable of analyzing millions of DNA fragments simultaneously. It's used for comprehensive genetic screening to identify mutations across all protein-coding regions (exome) or the entire genetic makeup (genome).

Cytogenetics:

Karyotyping: this traditional method examines the number and structure of chromosomes under a microscope, identifying abnormalities like extra chromosomes or translocations that can lead to diseases such as Down syndrome or chronic myelogenous leukemia.

Fluorescence In Situ Hybridization (FISH): FISH uses fluorescent probes to illuminate specific gene segments on chromosomes, useful for identifying gene amplifications or deletions.

Microarrays: this technology assesses DNA for duplications, deletions, or large identical DNA stretches using fluorescently labeled DNA samples hybridized on a chip, providing detailed chromosomal information.

Gene Expression Profiling: this test measures which genes are active in cells, using RNA from a tissue sample to determine gene activity. It's particularly used in cancer to guide treatment decisions based on the genes expressed by a tumor.

Each of these technologies plays a crucial role in diagnosing genetic disorders, guiding treatment decisions, and advancing our understanding of genetic diseases.

Sample Types

Samples typically include blood, saliva, or tissue samples containing DNA.  Sample collection can be as simple as performing a cheek swab or collecting saliva.

Interpretation of Test Results

Interpreting test results for 13q14.3 abnormalities requires expertise and an understanding of genetic principles. A positive result indicating a deletion or duplication in the 13q14.3 region may suggest an increased risk of certain genetic disorders or predisposition to specific health conditions. 

However, the clinical significance of these findings can vary depending on factors such as the size and location of the genetic alteration, as well as the presence of other genetic or environmental factors. 

Genetic counseling is often recommended to help patients and their families understand the implications of test results and make informed decisions regarding healthcare management and treatment options.

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