Appendix
Human Diseases Cited in the Main Text, in Which Junk DNA Has Been Implicated
Alzheimer’s disease   May involve over-expression of an antisense RNA that binds to and stabilises the critical BACE1 mRNA.
Angelman syndrome   A condition caused by abnormal imprinting. Junk DNA is vital in control of imprinting, including the involvement of imprinting control regions, promoters, long non-coding RNAs and cross-talk with the epigenetic systems.
Aplastic anaemia   Around 5 per cent of cases are caused by mutations in some of the critical genes that maintain the lengths of telomeres, the junk regions at the ends of chromosomes.
Basal cell carcinoma   A small number of cases are caused by mutations in the non-protein-coding region at the beginning of a gene, which result in decreased expression of the RNA from that gene.
Beckwith-Wiedemann syndrome   A condition caused by abnormal imprinting. Junk DNA is vital in control of imprinting, including the involvement of imprinting control regions, promoters, long non-coding RNAs and cross-talk with the epigenetic systems.
Burkitt’s lymphoma   Caused when the Myc oncogene from chromosome 8 gets translocated to chromosome 14 and placed under the control of the immunoglobulin promoter.
Cancer   Junk DNA has been implicated at a number of levels in cancer, such as over-expression of certain long non-coding RNAs in specific cancer types. In most cases, the evidence isn’t yet strong enough to determine how significant a role these play in human pathology. However, over-expression of the proteins that maintain the lengths of telomeres, the junk regions at the ends of chromosomes, are now generally accepted as having a causal role in the progression of some tumours. Mis-targeting of epigenetic enzymes to the wrong genes because of abnormal expression of long non-coding RNAs is also under active investigation as another method by which cancer cells proliferate abnormally.
Cartilage-hair hypoplasia   Caused by mutations which affect smallRNAs embedded within long non-coding RNAs.
Congenital diarrhoea disorder   Caused by a mutation in a splicing signal in a gene.
Cornelia de Lange syndrome   Caused by defects in a protein required for the junk-mediated higher-order structuring of DNA.
Down’s syndrome   Caused by uneven distribution of chromosome 21 to developing gametes, a process dependent on a junk region called the centromere.
Duchenne muscular dystrophy   Some cases are caused by mutations which result in abnormal splicing of the dystrophin RNA molecule.
Dyskeratosis congenita   Can be caused by mutations in a number of different genes, each of which is involved in maintaining the lengths of telomeres, the junk regions at the ends of chromosomes.
Edward’s syndrome   Caused by uneven distribution of chromosome 18 to developing gametes, a process dependent on a junk region called the centromere.
ETMR paediatric brain tumour   Caused by rearrangement and amplification of a smallRNA cluster.
Extra digits   Caused by single base changes in an enhancer for a morphogen.
Facioscapulohumeral muscular dystrophy   Caused by the interactions of a combination of junk DNA elements, leading to abnormal expression of a retroviral sequence.
Feingold syndrome   Some cases are caused by the loss of a cluster of smallRNAs.
Fragile X syndrome of mental retardation   Caused by the expansion of a CCG repeat in a non-protein-coding region at the beginning of a gene. The repeat prevents expression of the gene by making it difficult for the cell to copy the DNA into RNA.
Friedreich’s ataxia   Caused by the expansion of a GAA repeat in a non-protein-coding region within a gene. The repeat prevents expression of the gene by making it difficult for the cell to copy the DNA into RNA.
Hepatitis C virus   A smallRNA produced by human liver cells binds to the viral RNA, stabilising it and promoting viral productivity.
HHV-8 susceptibility   Can be caused by mutation in a splicing signal in a gene.
Holoprosencephaly   Some cases have been shown to be caused by mutations in an enhancer region for a morphogen.
Hutchinson-Gilford progeria   Caused by a mutation which creates an extra splicing signal in a gene.
Idiopathic pulmonary fibrosis   Can be caused by mutations in a number of different genes, each of which is involved in maintaining the lengths of telomeres, the junk regions at the ends of chromosomes.
IPEX autoimmune disorder   Caused by a mutation in the non-protein-coding region at the end of a gene, which prevents correct processing of the mRNA.
Malignant melanoma   A small number of cases are caused by mutations in the non-protein-coding region at the beginning of a gene, which result in the insertion of extra amino acids into the protein.
Myotonic dystrophy   Caused by the expansion of a CTG repeat in a non-protein-coding region at the end of a gene. The repeat is copied into RNA, and mops up RNA-binding proteins, resulting in mis-regulation of a large number of other mRNA molecules.
Neuropathic pain   May involve over-expression of a long non-coding RNA that regulates expression of a key ion channel.
North American eastern equine encephalitis virus   A smallRNA produced by human immune cells binds to the viral genome and prevents the immune system from recognising that the body is under attack.
Ohio Amish dwarfism   Caused by a mutation in a non-coding RNA required for the proper functioning of the splicing machinery.
Opitz-Kaveggia syndrome   Caused by defects in a protein that is critical for interaction with long non-coding RNAs in the Mediator complex.
Osteogenesis imperfecta (brittle bone disease)   A small number of cases are caused by mutations in the non-protein-coding region at the beginning of a gene, which result in the insertion of extra amino acids into the protein.
Pancreatic agenesis   Some cases have been shown to be caused by mutations in enhancer sequences.
Patau’s syndrome   Caused by uneven distribution of chromosome 13 to developing gametes, a process dependent on a junk region called the centromere.
Prader-Willi syndrome   A condition caused by abnormal imprinting. Junk DNA is vital in control of imprinting, including the involvement of imprinting control regions, promoters, long non-coding RNAs and cross-talk with the epigenetic systems.
Retinitis pigmentosa   Some cases are caused by a defect in a protein which is required to ensure normal splicing and removal of junk DNA from mRNA molecules.
Roberts syndrome   Caused by defects in a protein required for the junk-mediated higher-order structuring of DNA.
Silver-Russell syndrome   A condition caused by abnormal imprinting. Junk DNA is vital in control of imprinting, including the involvement of imprinting control regions, promoters, long non-coding RNAs and cross-talk with the epigenetic systems.
Spinal muscular atrophy   The SMN2 gene is unable to compensate for mutations in the closely related SMN1 gene, because of a variant base pair which prevents normal splicing of SMN2 mRNA into functional protein.
X0 syndrome (Turner’s syndrome)   Women with only one X chromosome, caused by uneven distribution of X chromosomes to developing gametes, a process dependent on a junk region called the centromere.
XXX syndrome   Women with three X chromosomes, caused by uneven distribution of X chromosomes to developing gametes, a process dependent on a junk region called the centromere.
XXY syndrome (Klinefelter’s syndrome)   Men with two X chromosomes, caused by uneven distribution of X chromosomes to developing gametes, a process dependent on a junk region called the centromere.