Chromosome 11

The following conditions are caused by changes in the structure or number of copies of chromosome 11.

Beckwith-Wiedemann syndrome

Beckwith-Wiedemann syndrome results from the abnormal regulation of genes on part of the short (p) arm of chromosome 11. The genes are located close together in a region designated 11p15.5 near the end of the chromosome.

People normally inherit one copy of chromosome 11 from each parent. For most genes on this chromosome, both copies of the gene are active, or "turned on," in cells. For some genes in the 11p15.5 region, however, only the copy inherited from a person's father (the paternal copy) is active. For other genes, only the copy inherited from a person's mother (the maternal copy) is active. These parent-specific differences in gene activation are caused by a phenomenon called genomic imprinting. Researchers have determined that changes in genomic imprinting disrupt the regulation of several genes located at 11p15.5, including CDKN1C, H19, IGF2, and KCNQ1OT1. Because these genes are involved in directing normal growth, problems with their regulation lead to overgrowth and the other characteristic features of Beckwith-Wiedemann syndrome.

Ten percent to twenty percent of cases of Beckwith-Wiedemann syndrome are caused by a genetic change known as paternal uniparental disomy (UPD). Paternal UPD causes people to have extra copies of genes that are active only on the paternal copy of the chromosome. People with paternal UPD are also missing genes that are active only on the maternal copy of the chromosome. In Beckwith-Wiedemann syndrome, paternal UPD usually occurs early in embryonic development and affects only some of the body's cells. This phenomenon is called mosaicism. Mosaic paternal UPD leads to an imbalance in active paternal and maternal genes on chromosome 11, which underlies the signs and symptoms of the disorder.

About 1 percent of all people with Beckwith-Wiedemann syndrome have a chromosomal abnormality such as a rearrangement (translocation) involving 11p15.5 or abnormal copying (duplication) of genetic material in this region. Like the other genetic changes responsible for Beckwith-Wiedemann syndrome, these changes disrupt the normal regulation of genes in this part of chromosome 11.

cancers

Changes in chromosome 11 have been identified in several types of human cancer. These genetic changes are somatic, which means they are acquired during a person's lifetime and are present only in certain cells. In some cases, translocations of genetic material between chromosome 11 and other chromosomes have been associated with cancers of blood-forming cells (leukemias) and cancers of immune system cells (lymphomas).

Translocations involving chromosome 11 have also been found in solid tumors such as Ewing sarcoma. Ewing sarcoma is a type of cancer that forms in the bones or soft tissues and occurs most often in children and young adults. The translocations responsible for Ewing sarcoma typically fuse the EWS gene on chromosome 22 with the FLI1 gene on chromosome 11. The protein produced from the abnormally fused EWS-FLI1 gene probably enhances changes that can lead to a cancerous tumor, such as uncontrolled cell division and cell growth.

Emanuel syndrome

Emanuel syndrome is caused by the presence of extra genetic material from chromosome 11 and chromosome 22 in each cell. In addition to the usual 46 chromosomes, people with Emanuel syndrome have an extra (supernumerary) chromosome consisting of a piece of chromosome 22 attached to a piece of chromosome 11. The extra chromosome is known as a derivative 22 or der(22) chromosome.

People with Emanuel syndrome typically inherit the der(22) chromosome from an unaffected parent. The parent carries a chromosomal rearrangement between chromosomes 11 and 22 called a balanced translocation. No genetic material is gained or lost in a balanced translocation, so these chromosomal changes usually do not cause any health problems. As the translocation is passed to the next generation, it can become unbalanced. Individuals with Emanuel syndrome inherit an unbalanced translocation between chromosomes 11 and 22 that introduces extra genetic material in the form of the der(22) chromosome.

As a result of the extra chromosome, people with Emanuel syndrome have three copies of some genes in each cell instead of the usual two copies. The excess genetic material disrupts the normal course of development, leading to intellectual disability and birth defects. Researchers are working to determine which genes are included on the der(22) chromosome and what role these genes play in development.

Russell-Silver syndrome

Like Beckwith-Wiedemann syndrome, Russell-Silver syndrome can result from changes in genes in the 11p15.5 region. Specifically, Russell-Silver syndrome has been associated with changes in genomic imprinting that affect the regulation of the H19 and IGF2 genes on chromosome 11. The changes are different from those seen in Beckwith-Wiedemann syndrome and have the opposite effect on growth. Although both disorders can be caused by abnormal regulation of these genes, the changes that cause Russell-Silver syndrome lead to slow growth and short stature instead of overgrowth.

other chromosomal conditions

Other changes in the number or structure of chromosome 11 can have a variety of effects, including intellectual disability, delayed development, slow growth, distinctive facial features, and weak muscle tone (hypotonia). Changes involving chromosome 11 include an extra piece of the chromosome in each cell (partial trisomy 11), a missing segment of the chromosome in each cell (partial monosomy 11), and a circular structure called a ring chromosome 11. Ring chromosomes occur when a chromosome breaks in two places and the ends of the chromosome arms fuse together to form a circular structure.

A condition called Jacobsen syndrome results from a deletion of genetic material from the end of the long (q) arm of chromosome 11 in each cell. This condition is also known as chromosome 11q deletion syndrome. Jacobsen syndrome is characterized by delayed development, an abnormal skull shape called trigonocephaly, a distinctive facial appearance, heart defects, and a reduction in the number of blood platelets (thrombocytopenia). The loss of several genes on the long arm of chromosome 11 is likely responsible for the varied features of Jacobsen syndrome.

Another condition, Potocki-Shaffer syndrome, is caused by the deletion of a segment of the short (p) arm of chromosome 11. This condition is also known as proximal 11p deletion syndrome (P11pDS). The characteristic features of Potocki-Shaffer syndrome include openings in the two bones that form the top and sides of the skull (enlarged parietal foramina), multiple benign bone tumors called exostoses, intellectual disability, delayed development, a distinctive facial appearance, and problems with vision. The features of Potocki-Shaffer syndrome result from the loss of several genes on the short arm of chromosome 11. Researchers have determined that the deletion of a gene called ALX4 causes enlarged parietal foramina in people with this condition, while the loss of another gene, EXT2, underlies the multiple exostoses. Researchers are working to find genes on the short arm of chromosome 11 that are associated with the other features of Potocki-Shaffer syndrome.

The deletion of another segment of the short (p) arm of chromosome 11 causes a disorder known as WAGR syndrome. The acronym WAGR stands for Wilms tumor (a rare form of kidney cancer), aniridia (an absence of the colored part of the eye, called the iris), genitourinary anomalies, and mental retardation (intellectual disability). These features result from the loss of several neighboring genes on the short arm of chromosome 11. A loss of the PAX6 gene disrupts normal eye development, leading to aniridia, and also affects the development of the brain. The deletion of another gene, WT1, greatly increases the risk of developing Wilms tumor and may underlie the genital and urinary tract abnormalities in this disorder.

Geneticists use diagrams called ideograms as a standard representation for chromosomes. Ideograms show a chromosome's relative size and its banding pattern. A banding pattern is the characteristic pattern of dark and light bands that appears when a chromosome is stained with a chemical solution and then viewed under a microscope. These bands are used to describe the location of genes on each chromosome.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

You may find the following resources about chromosome 11 helpful. These materials are written for the general public.

• Additional NIH Resources - National Institutes of Health
  • National Cancer Institute: Ewing Family of Tumors (http://www.cancer.gov/cancertopics/types/ewings/)
  • National Human Genome Research Institute: Chromosome Abnormalities (http://www.genome.gov/11508982)
• MedlinePlus - Health information
  Encyclopedia: Chromosome (http://www.nlm.nih.gov/medlineplus/ency/article/002327.htm)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

• Gene Reviews - Clinical summary
  • Gene Review: Beckwith-Wiedemann Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=bws)
  • Gene Review: Emanuel Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=emanuel)
  • Gene Review: Russell-Silver Syndrome (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=rss)
• Gene Tests - DNA tests ordered by healthcare professionals
  • Gene Test: Beckwith-Wiedemann Syndrome (http://www.genetests.org/query?testid=2905)
  • Gene Test: Jacobsen Syndrome (11q- Deletion Syndrome) (http://www.genetests.org/query?testid=2844)
  • Gene Test: Potocki-Shaffer Syndrome (11p11.2 Deletion Syndrome) (http://www.genetests.org/query?testid=74181)
  • Gene Test: Russell-Silver Syndrome (http://www.genetests.org/query?testid=9009)
  • Gene Test: WAGR Syndrome (http://www.genetests.org/query?testid=194100)
• Research Resources - Tools for researchers
  • Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Indexbychrom/idxa_11.html)
  • Cancer Genetics Web (http://www.cancerindex.org/geneweb/clinkc11.htm)
  • Database of Genomic Variants (http://projects.tcag.ca/variation/cgi-bin/tbrowse/tbrowse?source=hg17&table=Locus&show=table&keyword=&flop=AND&fcol=_C19&fcomp==&fkwd=chr11&cols=)
  • Ensembl Human Map View (http://www.ensembl.org/Homo_sapiens/mapview?chr=11)
  • Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. (http://www.nature.com/nature/journal/v440/n7083/full/nature04632.html)
  • Oak Ridge National Laboratory (http://genome.ornl.gov/cgi-bin/GCat/GetChrom.cgi?org=human&chr=11)
  • The Sanger Institute: Human Chromosome 11 Project Overview (http://www.sanger.ac.uk/HGP/Chr11/)
  • U.S. Department of Energy: Human Chromosome Launchpad (http://www.ornl.gov/sci/techresources/Human_Genome/launchpad/chrom11.shtml)
• PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed&term=(Chromosomes,+Human,+Pair+11[MAJR])+AND+(Chromosome+11[TI])+AND+english[la]+AND+human[mh]&orig_db=PubMed&filters=ON&pmfilter_EDatLimit=1800+Days)
• OMIM - Genetic disorder catalog
  • OMIM: Ewing Sarcoma Breakpoint Region 1 (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=133450)
  • OMIM: Jacobsen Syndrome (Chromosome 11q Deletion Syndrome) (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147791)
  • OMIM: Potocki-Shaffer Syndrome (Chromosome 11p11.2 Deletion Syndrome) (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601224)
  • OMIM: WAGR Syndrome (http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=194072)
• Map Viewer - Genetic maps (http://www.ncbi.nlm.nih.gov/mapview/maps.cgi?org=human&maps=ideogr,morbid,pheno&zoom=100&chr=11)

base pair ; benign ; blood platelets ; cancer ; cell ; cell division ; chromosome ; contiguous ; contiguous genes ; contiguous gene syndrome ; deletion ; DNA ; duplication ; embryonic ; Exostoses ; gene ; hypotonia ; immune system ; imprinting ; kidney ; leukemia ; lymphoma ; maternal ; mental retardation ; monosomy ; mosaic ; mosaicism ; muscle tone ; peripheral ; platelets ; protein ; proximal ; rearrangement ; receptor ; ring chromosomes ; sarcoma ; short stature ; sign ; soft tissue ; stature ; symptom ; syndrome ; thrombocytopenia ; tissue ; translocation ; trisomy ; tumor ; uniparental disomy ; Wilms tumor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).