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Chromosome 1
The largest human chromosome - ~8% of the genome and the most gene-dense by absolute count.
Schematic of chromosome 1 showing the short (p) and long (q) arms. Arm ratio per GRCh38 - banding schematic.
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Overview
Chromosome 1 stands as the largest of the 23 human chromosome pairs, containing approximately 249 million base pairs of DNA. This substantial size translates to around 8% of the total genetic material in each human cell, and the chromosome carries an estimated 2,000 or more protein-coding genes, the highest absolute gene count of any chromosome. Because of this density, chromosome 1 contributes to an exceptionally broad range of biological processes, from fundamental metabolism and structural support to immune regulation and cardiovascular health.
The chromosome features a metacentric structure, meaning its centromere sits near the middle, dividing the chromosome into a short arm (designated 1p) and a long arm (1q) of roughly similar lengths. This balanced architecture becomes visible under the microscope during cell division, when the DNA condenses into its characteristic X-shaped form. Clinically, chromosome 1 is notable for microdeletion syndromes affecting early development, recurrent copy-number variants influencing neurodevelopmental outcomes, and a wealth of single-gene disorders spanning cardiac arrhythmias, metabolic disease, and cancer predisposition.
Within the NHS Genomic Medicine Service, chromosome 1 features prominently in both rare-disease diagnostics and common-disease genomics. Chromosomal microarray analysis can detect structural rearrangements such as 1p36 deletions, while targeted gene panels and whole-genome sequencing identify pathogenic variants in individual genes. The breadth of conditions linked to this chromosome underscores its central role in human health and development.
Structure
Like all human chromosomes, chromosome 1 consists of a single, enormously long DNA molecule wound around histone proteins to form nucleosomes. These bead-on-a-string structures coil further into chromatin fibres, which in turn fold and compact during cell division to produce the dense, rod-like chromosome visible under a light microscope. The centromere, positioned near the midpoint in this metacentric chromosome, serves as the attachment site for spindle fibres that pull sister chromatids apart during mitosis and meiosis, ensuring each daughter cell receives an accurate copy.
The short arm, 1p, and the long arm, 1q, each span over 100 million base pairs and contain distinct clusters of genes and regulatory elements. The p arm extends from the centromere to the telomere at 1p36, while the q arm reaches to the telomere at 1q44. Both arms contain euchromatin, gene-rich regions that remain relatively open and accessible for transcription, interspersed with heterochromatin, more tightly packed stretches that are generally less active. Because chromosome 1 is not acrocentric, it lacks the ribosomal RNA gene clusters found on the short arms of chromosomes 13, 14, 15, 21, and 22. Instead, its short arm carries a full complement of protein-coding genes, contributing to the chromosome's status as the most gene-dense by total count.
Video: What is a karyotype?
Notable regions
The 1p36 region, at the tip of the short arm, has long been recognised for its clinical significance. Terminal deletions of 1p36 result in 1p36 deletion syndrome, one of the more common subtelomeric microdeletion syndromes. Children with this deletion typically present with developmental delay, intellectual disability, distinctive facial features, and sometimes structural heart defects or seizures. The size of the deletion varies, but most span several million base pairs and remove dozens of genes, making it difficult to pinpoint a single culprit. The syndrome is usually detected through chromosomal microarray, and families are offered genetic counselling through NHS clinical genetics services to discuss recurrence risk and management.
Further along the short arm, the 1p13.3 region has gained attention from genome-wide association studies as a hotspot for variants influencing low-density lipoprotein cholesterol levels. Genes in this region, including PSRC1 and SORT1, have been linked to cardiovascular disease risk in large population studies. While these associations reflect common genetic variation rather than rare pathogenic variants, they illustrate how certain chromosomal regions contribute to widespread traits and common conditions. On the long arm, 1q21.1 harbours a recurrent microdeletion and microduplication syndrome. Deletions and duplications in this region arise from non-allelic homologous recombination between flanking repetitive sequences, producing copy-number changes that associate with variable neurodevelopmental outcomes, including autism spectrum features, learning difficulties, and congenital anomalies. Because penetrance is incomplete and expressivity highly variable, some carriers have minimal or no apparent symptoms, complicating genetic counselling.
Another notable locus sits at 1q32.1, where the CFH gene encodes complement factor H, a regulator of the immune system's complement pathway. Common variants in CFH significantly increase the risk of age-related macular degeneration, a leading cause of vision loss in older adults. This region exemplifies how chromosome 1 contributes not only to rare Mendelian disorders but also to the genetic architecture of common, multifactorial conditions. Across both arms, the chromosome contains numerous other genes implicated in cancer predisposition, metabolic disorders, and structural protein defects, making it a focal point for clinical genomics.
Notable genes
Chromosome 1 hosts several genes that feature regularly in clinical genetics referrals and research literature. MTHFR, located at 1p36.22, encodes methylenetetrahydrofolate reductase, an enzyme involved in folate metabolism. Variants in MTHFR can influence circulating folate levels and homocysteine concentrations, with ongoing debate about their relevance to cardiovascular risk and pregnancy outcomes, though major clinical guidelines do not currently recommend testing or treatment based on common MTHFR variants alone. LMNA, at 1q22, provides instructions for lamin A and lamin C, structural proteins that support the nuclear envelope. Pathogenic variants in LMNA cause a spectrum of conditions collectively termed laminopathies, including dilated cardiomyopathy, Emery-Dreifuss muscular dystrophy, and Hutchinson-Gilford progeria syndrome. The diversity of phenotypes reflects the protein's role in multiple tissues and its interactions with chromatin and signalling pathways.
RYR2, situated at 1q43, encodes the ryanodine receptor 2, a calcium-release channel essential for cardiac muscle contraction. Variants in RYR2 are a leading cause of catecholaminergic polymorphic ventricular tachycardia, an inherited arrhythmia syndrome triggered by exercise or emotional stress. PCSK9, at 1p32.3, produces a protease that regulates the number of low-density lipoprotein receptors on liver cells, directly influencing blood cholesterol levels. Loss-of-function variants in PCSK9 confer protection against coronary artery disease, a discovery that led to the development of PCSK9-inhibitor drugs now used in managing familial hypercholesterolaemia and refractory hyperlipidaemia. GBA, located at 1q22, encodes the lysosomal enzyme glucocerebrosidase. Biallelic pathogenic variants cause Gaucher disease, a lysosomal storage disorder, while heterozygous GBA variants are recognised as the strongest common genetic risk factor for Parkinson disease, illustrating how single genes can influence multiple conditions through different mechanisms.
Chromosomal disorders
Whole-chromosome aneuploidy of chromosome 1 - either trisomy 1 or monosomy 1 - is generally incompatible with survival beyond early embryonic development, reflecting the critical importance and dosage sensitivity of the genes it carries. As a result, clinically significant chromosomal disorders involving chromosome 1 arise instead from structural rearrangements, particularly deletions and duplications of specific regions.
1p36 deletion syndrome represents one of the most common terminal deletion syndromes, with an estimated prevalence of approximately one in 5,000 to one in 10,000 live births, though ascertainment varies. The deletion typically occurs de novo, meaning it arises as a new event during the formation of a parent's egg or sperm cell rather than being inherited. Most affected children present in infancy or early childhood with developmental delay, intellectual disability, hypotonia, feeding difficulties, and a constellation of distinctive facial features. Structural heart defects occur in a substantial minority, and seizures are common. The variability in severity partly reflects differences in deletion size and the specific genes involved. Diagnosis is usually made through chromosomal microarray analysis, and families are referred to NHS clinical genetics services for counselling and coordination of multidisciplinary care.
1q21.1 microdeletion and microduplication syndromes arise from recurrent structural variation at 1q21.1, mediated by regions of highly similar DNA sequence that flank the interval. Both deletions and duplications are associated with increased risk of developmental delay, learning difficulties, autism spectrum features, and minor physical anomalies such as distinctive facial features or skeletal findings. However, penetrance is incomplete - some individuals carrying these copy-number changes have no obvious medical or developmental concerns, while others experience significant impairment. This variability makes genetic counselling complex, particularly when a parent is found to carry the same rearrangement. Chromosomal microarray can identify these changes, often as part of a diagnostic work-up for developmental delay or as an incidental finding during prenatal testing. The NHS Genomic Medicine Service provides access to clinical genetics specialists who can help families interpret these findings in the context of the specific clinical picture and family history.
Prenatal screening & diagnosis
Because whole-chromosome trisomy or monosomy of chromosome 1 is not viable, this chromosome does not feature in the non-invasive prenatal testing panels used to screen for the common aneuploidies (trisomies 13, 18, and 21). However, structural abnormalities of chromosome 1, such as the 1p36 deletion, may be detected during pregnancy through several routes. If a routine anomaly scan identifies structural findings such as a heart defect or growth restriction, further testing with chromosomal microarray or karyotyping may be offered following invasive sampling through chorionic villus sampling or amniocentesis.
Chromosomal microarray analysis has become the first-tier test for pregnancies with ultrasound abnormalities, as it can detect submicroscopic deletions and duplications, including 1p36 and 1q21.1 rearrangements, that would be missed by conventional karyotyping. When a fetus is found to carry a copy-number variant on chromosome 1, parents are referred to a foetal medicine specialist and a clinical geneticist for counselling. The discussion typically covers the range of possible outcomes, acknowledging the variable expressivity and incomplete penetrance that characterise many of these rearrangements. Postnatal follow-up and developmental surveillance are arranged to provide early intervention and support as needed. For families with a known chromosome 1 rearrangement from a previous pregnancy or an affected family member, prenatal diagnosis can be offered in subsequent pregnancies if desired, through invasive testing and targeted analysis of the relevant region.
Inheritance & recurrence
Most clinically significant chromosomal abnormalities involving chromosome 1, including 1p36 deletions and 1q21.1 microdeletions or microduplications, arise de novo rather than being inherited from a parent. When a structural rearrangement occurs as a new event, the recurrence risk in future pregnancies is generally low, typically quoted at around 1%, reflecting the small possibility of parental germline mosaicism. However, if either parent carries a balanced chromosomal rearrangement, such as a translocation involving chromosome 1, the risk of an unbalanced outcome in offspring can be substantially higher, and detailed cytogenetic analysis of both parents is usually recommended after a child is diagnosed with a structural chromosome abnormality.
For single-gene disorders caused by pathogenic variants in genes on chromosome 1, the inheritance pattern depends on the specific gene and condition. Many of the well-characterised disorders follow autosomal dominant inheritance, meaning a single pathogenic variant is sufficient to cause disease, with a 50% recurrence risk for each future child if a parent carries the variant. Examples include RYR2-related catecholaminergic polymorphic ventricular tachycardia and LMNA-related dilated cardiomyopathy. Other conditions, such as Gaucher disease caused by biallelic GBA variants, follow autosomal recessive inheritance, with a 25% recurrence risk when both parents are carriers. Families in which a chromosome 1 abnormality or single-gene disorder has been identified are offered genetic counselling through the NHS to discuss inheritance patterns, recurrence risks, reproductive options such as preimplantation genetic testing, and the availability of prenatal diagnosis in future pregnancies. Tailored advice takes into account the specific variant, the family history, and the individual family's values and preferences.
Frequently asked questions
What is 1p36 deletion syndrome and how is it diagnosed?
1p36 deletion syndrome arises when a small piece of the tip of the short arm of chromosome 1 is missing. It typically causes developmental delay, intellectual disability, distinctive facial features, and sometimes heart defects or seizures. Diagnosis is usually made through chromosomal microarray analysis, which can detect these submicroscopic deletions. Most cases occur spontaneously rather than being inherited.
Can chromosome 1 abnormalities be detected before birth?
Structural abnormalities of chromosome 1, such as deletions or duplications, can sometimes be suspected if a routine pregnancy ultrasound shows findings such as heart defects or growth concerns. Definitive diagnosis requires invasive testing through chorionic villus sampling or amniocentesis, followed by chromosomal microarray or karyotype analysis. Non-invasive prenatal testing does not screen for chromosome 1 abnormalities, as whole-chromosome aneuploidy of chromosome 1 is not compatible with ongoing pregnancy.
If my child has a 1q21.1 deletion, what does that mean for their development?
The 1q21.1 microdeletion is associated with variable outcomes. Some children experience developmental delay, learning difficulties, or autism spectrum features, while others develop typically. Because the same deletion can produce different effects in different individuals, it is difficult to predict the exact outcome at the time of diagnosis. Your clinical genetics team and paediatrician will arrange developmental monitoring and early intervention services tailored to your child's specific needs.
Are genetic conditions caused by chromosome 1 genes usually inherited?
It depends on the specific condition. Structural abnormalities such as 1p36 deletions usually occur spontaneously, with low recurrence risk in future pregnancies. Single-gene disorders on chromosome 1 follow various inheritance patterns: some are autosomal dominant, requiring only one pathogenic variant to cause disease, while others are autosomal recessive, requiring variants in both gene copies. Your clinical genetics team can clarify the inheritance pattern relevant to your family and discuss recurrence risks and reproductive options.
Why does chromosome 1 carry so many genes compared to other chromosomes?
Chromosome 1 is simply the largest chromosome by physical size, spanning roughly 249 million base pairs, so it has the space to accommodate more genes. The distribution of genes across the genome is not uniform - some regions are gene-rich while others contain fewer genes and more repetitive DNA. Chromosome 1's substantial gene count reflects both its size and its relatively high gene density, particularly in certain regions of both the short and long arms.
Launch-set genes on chromosome 1
Genes on this chromosome that currently have dedicated pages in the library. This list grows as we publish more.