Chromosomes are vital components of eukaryotic or prokaryotic cells, in which an entire genome is stored. Aside from the gametes, human cells (autosomes) each contain 23 pairs of chromosomes, giving a total of 46 chromosomes per cell. Male and female gametes have only one copy of each of the 23 chromosomes rather than pairs, and only form a cell that has the complete set of chromosomes after they unite in fertilization.
In a process called karyotyping, the pairs of autosomal chromosomes can be ordered, classified and numbered according to their size and the twenty-third pair are the sex chromosomes (XX for females and XY for males).
Chromosome 1 is the largest human chromosome, made up of around 249 million nucleotide base pairs and representing approximately 8% of the entire DNA within a human cell. Research into chromosome 1 has shown that it contains around 4,220 genes and was the last gene to have its DNA sequencing completed by The Human Genome Project, nearly twenty years back. The proteins these genes code for perform a variety of essential roles in the body.
As the largest chromosome, chromosome 1 is the most susceptible to polymorphisms or mutations. Polymorphisms are variations of the chromosomal base pairs that are present in at least 1% of the general population. Polymorphisms can involve one or more base pairs. When they involve single nucleotides, they are termed single nucleotide polymorphisms (SNPs). On Chromosome 1, there are an estimated 740,000 SNPs and it is thought that at least 22 loci are polymorphic among the European population.
A wide range of disorders and abnormalities can therefore be attributed to variations at the loci of chromosome 1. More than 350 diseases have been linked to abnormalities in the sequence of chromosome 1 including cancers, mendelian disorders and various developmental and neurological diseases where the causative gene mutations have not yet been identified.
Changes to the structure or number of chromosomes can also cause a variety of diseases and developmental disorders. Below are some examples of the conditions that occur when these changes affect chromosome 1.
1p36 deletion syndrome
This syndrome is caused by the deletion of genetic material on a particular region of the short (p) arm of chromosome 1. Symptoms of the condition include impaired intellectual ability, characteristic facial features and are likely to be linked to the deletion of multiple genes across this chromosomal region.
This condition has also been associated with deletions that occur in the 1p36 region of chromosome 1. In this illness, a cancerous tumor develops that is made up of immature neurons, called neuroblasts. Around a quarter of affected individuals have a deletion that spans 1p36.1 – 1p36.3, which causes a more severe from of the condition. Researchers believe the deletion affects an area containing a gene that prevents abnormal cell division and proliferation. These genes are referred to as tumor suppressor genes. The deletion of tumor suppressor genes in this way can lead to abnormal cell growth and cancer.
This chromosomal change involves deletion of a small portion of the long (q) arm of chromosome 1, with around 1.35 million DNA base pairs or 1.35 megabases (Mb) going missing in the q21.1 region of the chromosome. Exactly how large the deletion is varies, but usually, at least nine genes are contained in the region. Signs of the disease such as developmental delay, impaired intellectual ability and physical, neurological and psychological problems are probably associated with the loss of several genes in this region.