Notes on Thrombophilia Genetic Disorders
I'm currently researching thrombophilia, and Genomic locations for root causes. This is in preparation for a Whole Genome Sequencing.
Factor V Leiden Thrombophilia
Effect:
The coagulation system is controlled by several proteins, including a protein called activated protein C (APC). APC normally inactivates coagulation factor V, which slows down the clotting process and prevents clots from growing too large. However, in people with factor V Leiden thrombophilia, coagulation factor V cannot be inactivated normally by APC. As a result, the clotting process remains active longer than usual, increasing the chance of developing abnormal blood clots. -- NIH.gov
Location:
Cytogenetic Location: 1q24.2, which is the long (q) arm of chromosome 1 at position 24.2
Molecular Location: base pairs 169,511,954 to 169,586,630 on chromosome 1
-- NIH.gov
Frequency: 3-8% with European or Middle Eastern Ancestry
Between 3 and 8 percent of people with European ancestry carry one copy of the factor V Leiden mutation in each cell, and about 1 in 5,000 people have two copies of the mutation.
--NIH.gov
Prothombin gene mutation
Effect:
The protein produced from the F2 gene, prothrombin (also called coagulation factor II), is the precursor to a protein called thrombin that initiates a series of chemical reactions in order to form a blood clot. The particular mutation that causes prothrombin thrombophilia results in an overactive F2 gene that causes too much prothrombin to be produced. An abundance of prothrombin leads to more thrombin, which promotes the formation of blood clots.
--NIH.gov
Location:
Cytogenetic Location: 11p11.2, which is the short (p) arm of chromosome 11 at position 11.2
Molecular Location: base pairs 46,719,166 to 46,739,508 on chromosome 11
--NIH.gov
Frequency: 2% of white americans
Approximately 1 in 50 people in the white population in the United States and Europe has prothrombin thrombophilia.
Antithrombin deficiency (Antithrombin III)
Effect:
This gene provides instructions for producing a protein called antithrombin (previously known as antithrombin III). This protein is found in the bloodstream and is important for controlling blood clotting. Antithrombin blocks the activity of proteins that promote blood clotting, especially a protein called thrombin. Most of the mutations that cause hereditary antithrombin deficiency change single protein building blocks (amino acids) in antithrombin, which disrupts its ability to control blood clotting. Individuals with this condition do not have enough functional antithrombin to inactivate clotting proteins, which results in the increased risk of developing abnormal blood clots. --NIH.gov
Location:
Cytogenetic Location: 1q25.1, which is the long (q) arm of chromosome 1 at position 25.1
Molecular Location: base pairs 173,903,804 to 173,917,378 on chromosome 1
--NIH.gov
Frequency: ~0.04% of humans
Notes:
...typically inherited in an autosomal dominant pattern, which means one altered copy of the SERPINC1 gene in each cell is sufficient to cause the disorder. Inheriting two altered copies of this gene in each cell is usually incompatible with life --NIH.gov
Protein C
Effect:
Most of the mutations that cause protein C deficiency change single protein building blocks (amino acids) in protein C, which disrupts its ability to control blood clotting. Individuals with this condition do not have enough functional protein C to inactivate clotting proteins, which results in the increased risk of developing abnormal blood clots. Protein C deficiency can be divided into type I and type II based on how mutations in the PROC gene affect protein C. Type I is caused by PROC gene mutations that result in reduced levels of protein C, while type II is caused by PROC gene mutations that result in the production of an altered protein C with reduced activity. Both types of mutations can be associated with mild or severe protein C deficiency; the severity is determined by the number of PROC gene mutations an individual has. --NIH.gov
Frequency: 2% of humans
Location:
Cytogenetic Location: 2q14.3, which is the long (q) arm of chromosome 2 at position 14.3 Molecular Location: base pairs 127,418,143 to 127,429,246 on chromosome 2 --NIH.gov
Protein S
Effect:
Most mutations that cause protein S deficiency change single protein building blocks (amino acids) in protein S, which disrupts its ability to control blood clotting. Individuals with this condition do not have enough functional protein S to inactivate clotting proteins, which results in the increased risk of developing abnormal blood clots. Protein S deficiency can be divided into types I, II and III based on how mutations in the PROS1 gene affect protein S. -- NIH.gov
Frequency: 2% of humans
Location:
Cytogenetic Location: 3q11.1, which is the long (q) arm of chromosome 3 at position 11.1
Molecular Location: base pairs 93,873,037 to 93,974,090 on chromosome 3
-- NIH.gov
Thrombophilia due to thrombomodulin defect
Effect:
Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated.
--UNIPROT
Frequency:
Location:
Cytogenetic Location: 20p11.21, which is the short (p) arm of chromosome 20 at position 11.21
Molecular Location: base pairs 23,045,633 to 23,049,664 on chromosome 20
--NIH.gov