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Chromosome 20
Compact metacentric - home of PRNP (prion diseases) and JAG1 (Alagille syndrome).
Schematic of chromosome 20 showing the short (p) and long (q) arms. Arm ratio per GRCh38 - banding schematic.
Available at Jeen Health
Clinical tests that include this
Overview
Chromosome 20 is a metacentric chromosome, meaning its centromere sits close to the middle and divides the chromosome into two arms of roughly equal length. With 64.4 million base pairs, it represents approximately 2% of the total DNA in a human cell and carries around 544 protein-coding genes. Though neither the largest nor the smallest autosome, chromosome 20 punches above its weight clinically: it harbours genes responsible for a distinctive liver-and-vascular malformation syndrome, rare neurodegenerative prion diseases, and a form of inherited diabetes that typically presents in adolescence or young adulthood.
Because chromosome 20 is metacentric, the short arm (designated 20p) and the long arm (20q) are similar in size, giving the chromosome a relatively symmetrical appearance under the microscope during cell division. This balanced structure means no single arm dominates, and important genes are distributed across both. NHS laboratories routinely analyse chromosome 20 by karyotyping when constitutional chromosomal rearrangements are suspected, and by chromosomal microarray or targeted gene panels when clinical features point toward one of the well-characterised single-gene disorders on this chromosome.
Unlike the acrocentric chromosomes, chromosome 20 does not carry ribosomal RNA gene clusters on its short arm, and unlike the X and Y chromosomes it does not participate in sex determination. Its clinical significance lies almost entirely in the individual genes it carries rather than in whole-chromosome or segmental imbalances, which are exceptionally rare for chromosome 20.
Structure
Every chromosome consists of a single, enormously long molecule of DNA tightly packaged with proteins. The DNA double helix first wraps around histone proteins to form nucleosomes, which resemble beads on a string. These nucleosomes then coil into a fibre of chromatin, and during cell division the chromatin condenses further into the compact X-shaped structure visible under a microscope. The centromere is the pinched region where spindle fibres attach to pull the duplicated chromosomes apart into daughter cells. On chromosome 20, the centromere sits near the middle, creating a metacentric chromosome with a short arm (p, from the French *petit*) and a long arm (q, the next letter in the alphabet).
The short arm, 20p, stretches from the tip (the telomere at 20p13) down to the centromere and contains several hundred genes, including PRNP at 20p13 and JAG1 at 20p12.2. The long arm, 20q, extends from the centromere to the opposite telomere at 20q13.33 and likewise carries hundreds of genes, among them the imprinted GNAS locus at 20q13.13 and HNF4A at 20q13.12. Telomeres, the repetitive DNA sequences capping both ends, protect the chromosome from degradation and prevent the cell from mistaking a natural chromosome end for a DNA break. Together, this architecture ensures that chromosome 20 replicates faithfully and segregates correctly at every cell division, maintaining genomic stability across tissues and generations.
Video: What is a karyotype?
Notable regions
The band 20p13 near the tip of the short arm contains PRNP, the gene encoding the prion protein. In its normal form, this protein is found on the surface of neurons and may play a role in cell signalling and copper metabolism, though its precise function remains debated. Pathogenic variants in PRNP cause a group of rare neurodegenerative disorders collectively known as prion diseases, including familial Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. These conditions are characterised by progressive dementia, ataxia, and behavioural changes, and they differ from most genetic disorders in that the abnormal protein can sometimes propagate misfolding in other prion molecules, leading to the transmissible forms seen in sporadic and acquired Creutzfeldt-Jakob disease. NHS neurology and clinical genetics teams manage families with inherited prion disease, offering predictive testing and counselling where appropriate.
Further down the short arm at 20p12.2 lies JAG1, which encodes a cell-surface protein called Jagged-1 that participates in the Notch signalling pathway. This pathway is essential during embryonic development for the proper formation of blood vessels, the heart, the skeleton, and the bile ducts within the liver. Pathogenic loss-of-function variants in JAG1 account for the majority of cases of Alagille syndrome, a multisystem disorder characterised by bile-duct paucity leading to cholestasis and jaundice, heart defects (commonly peripheral pulmonary stenosis), skeletal abnormalities (butterfly vertebrae), eye findings (posterior embryotoxon), and distinctive facial features. Alagille syndrome shows autosomal dominant inheritance with variable expressivity, meaning that even within the same family, severity can range from life-threatening liver disease requiring transplantation to mild or subclinical findings. Diagnosis typically involves liver biopsy, echocardiography, and molecular testing of JAG1, all available through NHS hepatology and genetics services.
On the long arm at 20q13.13 sits GNAS, an imprinted gene that encodes the alpha subunit of a stimulatory G protein involved in hormone signalling. Imprinting means that only one copy of the gene (in this case, usually the maternally inherited copy for some transcripts) is active, while the other is silenced by chemical marks. Pathogenic variants in GNAS can cause pseudohypoparathyroidism, a group of disorders in which the body fails to respond properly to parathyroid hormone, leading to low blood calcium, high blood phosphate, and sometimes resistance to other hormones such as thyroid-stimulating hormone. The clinical picture depends on whether the variant arose on the maternal or paternal chromosome, illustrating the functional importance of genomic imprinting. Individuals may present with short stature, round face, brachydactyly (short fingers and toes), and subcutaneous ossifications. NHS endocrinology teams manage calcium and hormone replacement, while clinical genetics input helps clarify inheritance risks for relatives.
Notable genes
Beyond the genes already highlighted in specific cytogenetic bands, chromosome 20 is home to HNF4A at 20q13.12, a transcription factor that regulates genes involved in glucose metabolism and insulin secretion in pancreatic beta cells. Heterozygous pathogenic variants in HNF4A cause maturity-onset diabetes of the young type 1, often abbreviated as MODY1 or HNF4A diabetes. Unlike the more common forms of diabetes (type 1 and type 2), MODY1 typically presents in adolescence or early adulthood with mild to moderate hyperglycaemia that may initially respond to low-dose sulfonylurea tablets rather than insulin. Because MODY1 follows autosomal dominant inheritance, affected individuals have a 50% chance of passing the variant to each child, making cascade genetic testing in families particularly valuable for early diagnosis and tailored management. NHS diabetes services increasingly incorporate genetic testing for monogenic diabetes to distinguish MODY from type 1 or type 2 diabetes, which can substantially alter treatment.
Another gene on the long arm, ADA at 20q13.12, encodes an enzyme critical to purine metabolism and immune function. Severe combined immunodeficiency due to ADA deficiency is a life-threatening condition characterised by profound T-cell, B-cell, and natural-killer-cell defects, leaving affected infants highly susceptible to infections. Enzyme replacement therapy and haematopoietic stem-cell transplantation are treatment options, and ADA deficiency was one of the first diseases treated experimentally with gene therapy.
Chromosomal disorders
Whole-chromosome gains or losses involving chromosome 20 are exceptionally rare and typically seen only in mosaic form or in the context of complex chromosomal rearrangements. Trisomy 20 mosaicism has been reported in liveborn infants, often detected prenatally by amniocentesis or chorionic-villus sampling, but the clinical significance is highly variable and depends on the proportion of trisomic cells in different tissues. Some individuals are phenotypically normal, while others may exhibit growth restriction, developmental delay, or minor dysmorphic features. Because complete constitutional trisomy 20 is incompatible with survival to term, most cases represent confined placental mosaicism or low-level mosaicism in the fetus. NHS foetal medicine teams counsel families that a finding of trisomy 20 mosaicism on prenatal testing warrants careful follow-up, including detailed ultrasound assessment and postnatal karyotyping, but that outcomes are difficult to predict.
Microdeletions and microduplications involving chromosome 20 are also uncommon compared with other chromosomes. When they do occur, the clinical phenotype depends on the size and gene content of the imbalanced segment. For example, submicroscopic deletions encompassing the JAG1 gene at 20p12.2 can cause Alagille syndrome indistinguishable from that caused by point mutations, and chromosomal microarray analysis is now a standard diagnostic tool when Alagille syndrome is suspected but no pathogenic variant is found by sequencing. Similarly, deletions or duplications affecting the GNAS locus may mimic or modify the phenotype of pseudohypoparathyroidism, depending on the parent of origin and which transcripts are disrupted. NHS cytogenetics laboratories use array comparative genomic hybridisation to detect these copy-number changes, which may be missed by conventional karyotyping.
Prenatal screening & diagnosis
Because whole-chromosome abnormalities of chromosome 20 are so rare, chromosome 20 is not included in the routine non-invasive prenatal testing panels offered by the NHS, which focus on the common aneuploidies of chromosomes 13, 18, and 21. However, when a structural anomaly is detected on antenatal ultrasound, particularly findings suggestive of Alagille syndrome such as congenital heart defects, or when there is a family history of a chromosome-20-related condition, targeted genetic testing or chromosomal microarray may be offered through the NHS Foetal Medicine and Genomic Medicine services.
If a pathogenic variant in a gene on chromosome 20 is known in the family, such as a JAG1 variant causing Alagille syndrome or an HNF4A variant causing MODY1, preimplantation genetic testing or prenatal diagnosis by chorionic-villus sampling or amniocentesis can be arranged. These services are accessed via regional genetic counselling teams, who discuss the inheritance pattern, recurrence risk, and reproductive options. For conditions like Alagille syndrome with highly variable expressivity, families may weigh the unpredictability of outcome alongside the availability of medical and surgical management for affected children.
Inheritance & recurrence
Most pathogenic variants in chromosome 20 genes follow autosomal dominant inheritance, meaning that a single altered copy is sufficient to cause or predispose to disease. This is the pattern for JAG1 in Alagille syndrome, HNF4A in MODY1, and PRNP in familial prion disease. An affected parent has a 50% chance of passing the variant to each child, regardless of the child's sex. However, de novo variants, those arising for the first time in an individual with no family history, are common in Alagille syndrome: many cases represent new mutations in JAG1, in which case the recurrence risk for future siblings is low (though not zero, because of the theoretical possibility of parental germline mosaicism).
For imprinted loci such as GNAS, the inheritance pattern is more complex because the clinical phenotype depends on whether the variant is inherited from the mother or the father. In such cases, NHS clinical genetics services provide detailed counselling that takes into account the specific transcript affected, the parent of origin, and the family history. Predictive testing in at-risk relatives is available for many chromosome 20 conditions, particularly when early intervention can alter outcomes (as in MODY1, where recognising monogenic diabetes can avoid unnecessary insulin therapy). Families are encouraged to discuss these options with their regional genomic medicine service, which can coordinate testing, interpret results, and provide ongoing support.
Frequently asked questions
What is chromosome 20 best known for?
Chromosome 20 is particularly known for JAG1, pathogenic variants in which cause Alagille syndrome, a multisystem disorder affecting the liver, heart, and skeleton. It is also home to PRNP, the gene responsible for inherited prion diseases such as familial Creutzfeldt-Jakob disease, and to HNF4A, variants in which cause a form of young-onset diabetes called MODY1.
Can you have an extra or missing copy of chromosome 20?
Complete trisomy 20 (three copies instead of two) or monosomy 20 (one copy instead of two) is incompatible with development to term. Mosaic trisomy 20, in which only some cells carry an extra copy, is occasionally detected on prenatal testing and may be associated with variable outcomes, ranging from no apparent effect to growth restriction or developmental delay. Whole-chromosome abnormalities of chromosome 20 are exceptionally rare compared with trisomies 13, 18, and 21.
What is Alagille syndrome and how is it inherited?
Alagille syndrome is a genetic condition caused by pathogenic variants in JAG1 on chromosome 20p12.2. It affects multiple organ systems, most notably the liver (bile-duct paucity leading to jaundice), heart (pulmonary artery stenosis), skeleton (butterfly vertebrae), and eyes. It follows autosomal dominant inheritance, so an affected parent has a 50% chance of passing the variant to each child, though many cases arise as new mutations with no family history.
Is chromosome 20 tested during pregnancy?
Chromosome 20 is not part of the routine non-invasive prenatal testing offered by the NHS, which focuses on the common trisomies (13, 18, 21) and sometimes the sex chromosomes. However, if ultrasound findings raise concern for a condition linked to chromosome 20, such as Alagille syndrome, or if there is a known family history, targeted genetic testing or chromosomal microarray can be arranged through NHS Foetal Medicine services following discussion with a clinical geneticist or foetal-medicine consultant.
What should I do if a genetic change on chromosome 20 has been found in my family?
If a pathogenic variant in a chromosome 20 gene has been identified in a family member, ask your GP for a referral to your regional NHS clinical genetics service. The genetics team can confirm the diagnosis, explain the inheritance pattern and recurrence risks, discuss predictive or cascade testing for at-risk relatives, and coordinate specialist care where needed. Early diagnosis can be particularly beneficial for conditions like MODY1, where treatment differs from typical diabetes management.
Launch-set genes on chromosome 20
Genes on this chromosome that currently have dedicated pages in the library. This list grows as we publish more.