Chromosome 2

Chromosome 2 is the second largest human chromosome, spanning about 243 million DNA building blocks and containing 1,200 to 1,300 genes, with changes in its structure or number linked to various neurodevelopmental disorders, other conditions, and cancers.

Overview

Humans normally have 46 chromosomes in each cell, divided into 23 pairs. Two copies of chromosome 2, one copy inherited from each parent, form one of the pairs. Chromosome 2 is the second largest human chromosome, spanning about 243 million building blocks of DNA (base pairs) and representing almost 8 percent of the total DNA in cells.

Identifying genes on each chromosome is an active area of genetic research. Because researchers use different approaches to predict the number of genes on each chromosome, the estimated number of genes varies. Chromosome 2 likely contains 1,200 to 1,300 genes that provide instructions for making proteins. These proteins perform a variety of different roles in the body.

Health Conditions Related to Chromosomal Changes

The following chromosomal conditions are associated with changes in the structure or number of copies of chromosome 2.

2q37 deletion syndrome

2q37 deletion syndrome is caused by a deletion of genetic material near the end of the long (q) arm of chromosome 2, at a location designated 2q37. The signs and symptoms of this condition vary widely, but affected individuals generally have intellectual disability, behavioral problems, obesity, and skeletal abnormalities that often include unusually short fingers and toes (brachydactyly).

Researchers are working to identify all of the genes that contribute to the features of 2q37 deletion syndrome. While the size of the deletion varies among affected individuals, it always contains a certain gene, called HDAC4. The loss of this gene is thought to account for many of the characteristic features of 2q37 deletion syndrome, such as intellectual disability, behavioral problems, and skeletal abnormalities. Researchers are studying what role the other genes on 2q37 play in this disorder.

MBD5-associated neurodevelopmental disorder

Loss (deletion) or gain (duplication) of a small piece of chromosome 2 at position q23.1 can cause MBD5-associated neurodevelopmental disorder (MAND). MAND is a condition that affects neurological and physical development from birth. Affected individuals often have intellectual disability, developmental delay, impaired speech, sleep problems, distinctive facial features, and mild hand and foot abnormalities. Most people with MAND also have features similar to autism spectrum disorder, a developmental condition that affects communication and social interaction.

The chromosomal changes that can cause MAND are known as 2q23.1 microdeletions or 2q23.1 microduplications. The deleted or duplicated segment varies in size but always contains the MBD5 gene, and often additional genes. Most features of MAND are due to the loss or gain of one copy of the MBD5 gene. The MBD5 gene provides instructions for a protein that likely regulates the activity (expression) of genes, controlling the production of proteins that are involved in neurological functions such as learning, memory, and behavior.

Chromosome 2 deletions or duplications that cause MAND lead to an abnormal amount of MBD5 protein. Deletions prevent one copy of the MBD5 gene in each cell from producing any functional protein, which reduces the total amount of this protein in cells. Duplications lead to an increase in the amount of MBD5 protein.

It is likely that any changes in MBD5 protein levels impair its regulation of gene expression, leading to the uncontrolled production of certain proteins. Proteins that play a role in neurological functions are particularly affected, which helps explain why MAND impacts brain development and behavior. An increase or decrease in MBD5 protein disrupts gene expression that is normally well-controlled by this protein, which is likely why duplications and deletions of this gene lead to the same signs and symptoms.

The cause of the skeletal abnormalities and other non-neurological features of MAND is unclear. It is also unknown whether the loss or gain of other genes in chromosome