Inheritance

Children get LMBBS in the same way as they get blue or brown eyes, their father’s nose or their mother’s ears. The instructions for all of these things come in their genes- copies of instructions from their parents and their parents’ parents. There are some genes that are responsible for causing diseases, such as LMBBS.

LMBBS is a recessively inherited syndrome which occurs in about 1 in 100,000 people born in Northern Europe and America. That means that there will be about x people in the UK with LMBBS. Recessive inheritance means that a child has inherited two copies of a faulty gene, one from their mother and one from their father.

In most cases of LMBBS, both parents carry a normal gene (N), and a faulty, recessive gene (n). Although the parents have one copy of the faulty gene and are called carriers of the disease, they are unaffected by the presence of the faulty gene. We each carry two copies of every gene. For a recessive disease to occur, a child has to inherit two faulty copies of the gene; one from each parent.

Some types of LMBBS need mutations (the technical term for a faulty gene) in two separate genes. This means that in one of the LMBBS genes a patient has two faulty copies, and in another LMBBS gene he/she has one faulty copy and one normal copy. This is called triallelic inheritance (three alleles/mutations).

Parents who already have an affected child have a much higher chance of having further affected children and should have counseling on this. The child from each pregnancy has a 1 in 4 chance of being affected. If a new born child is not affected then there is a 2 in 3 chance that he/she will be a carrier of the gene for LMBBS.

LMBBS is rare; no one knows how many people carry mutations in an LMBBS gene without realizing but it is estimated to be approximately 1 in 160. Because genes are passed through families, the risk of having affected children is increased if a carrier marries within their family.

What is a gene?
Every cell in our bodies has genes. Genes carry instructions which influence how our cells and our bodies work.

A gene is a stretch of DNA located on our chromosomes. Chromosomes are found packaged into the nucleus of every single cell in our bodies. A particular stretch of DNA (gene) gives the cells instructions to make a particular type of protein. For example the gene for BBS1 (which is located on chromosome 11 of 23) encodes the information for the cell to make the BBS1 protein. Proteins are the chemicals that make things happen in our bodies.

A gene is the instructions needed for the cell to make a particular type of protein.

We inherit our genes from our parents, and we each have two copies of every gene, one coming from our mother and one from our father. The nucleus of each cell contains 23 pairs of chromosomes (23 inherited from our mother and 23 from our father).

These chromosomes are extremely long stands of DNA which are tightly packaged together. The DNA that the chromosomes are made from can be read by the cell to give the cell instructions to make all of the components (the proteins) it needs. Simply put, a gene codes for a protein.

Just like a house is made up of many individual bricks, humans are made up of millions of different types of cells. Although we have many different types of cells (i.e. skin cells, bone cells, blood cells), the cells themselves are made up of even smaller building blocks called proteins.

Sometimes mistakes occur in the DNA encoding a gene, these are called gene mutations. When these mistakes happen, the corresponding protein is often not formed correctly, and in some cases is not made at all. Depending on the severity of the mutation this can result in disease.

BBS genes and Proteins
So far scientists have identified 12 LMBBS genes. Scientist know that there are still more genes to find as not all patients have any of those 12 LMBBS genes faulty. This means that these patients must have mutations in other genes.

The table below shows all the different genes identified to date. The chromosome column shows which chromosome they are on (eg BBS1 is on Chromosome 11) and where they are on that chromosome. The % contribution column shows how likely it is for someone with LMBBS to have a mutation in this gene.

Gene Year Identified Chromosome % Contribution Protein Reference
BBS1 2002 11q13 20-40% Novel gene Nat Genet. 2002 Aug;31(4):435-8.
BBS2 2001 16q21 8-16% Novel gene Hum Mol Genet. 2001 Apr 1;10(8):865-74.
BBS3 2004 3p13 1% ARL6 Nat Genet. 2004 Sep;36(9):989-93.
BBS4 2001 15q23 1-3% TPRs/OGT Nat Genet. 2001 Jun;28(2):188-91.
BBS5 2004 2q31 1% Novel gene Cell. 2004 May 14;117(4):541-52.
BBS6/MKKS 2000 20p12 4-5% Chaperonin? Nat Genet. 2000 Sep;26(1):67-70.
BBS7 2003 4q27 1% Novel gene Am J Hum Genet. 2003 Mar;72(3):650-8.
BBS8 2003 14q32.1 2% PilF/TPRs Nature. 2003 Oct 9;425(6958):628-33.
BBS9 2005 7p14 2% PTH-B1 Am J Hum Genet. 2005 Dec;77(6):1021-33.
BBS10 2006 12q21.2 20% Chaperonin? Nat Genet. 2006 May;38(5):521-4.
BBS11 2006 9q33.1 - TRIM32 Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6287-92.
BBS12

The protein that these genes give instructions for is listed in the protein column. Scientists don’t yet know what the functions of most of these proteins are. However in the past few years people in Phils lab and other labs around the world have done a lot of work into establishing what these proteins do. Scientists are now certain that BBS proteins are involved in ciliary function. Currently more work is being carried out to fully determine the role these BBS proteins play in cells.

Other Pages in this section...

• Research
• Cilia
• Inheritance
• More than Meets the Eye
• Euro-Wabb