In this project, the primary goal was to find out the root genetic causes for pain by examining 2 big families afflicted with migraine and pain insensitivity. Pain is a key public health problem globally. Improved knowledge of the various types of pain and detection of susceptibility genes can help with enhanced treatments. Migraine is probably the most widespread neurovascular disorders, hurting a large part of people. The genetic contribution to migraine is approximately 50% based on family and twin studies. To spot novel susceptibility loci for migraine, we carried out a genome-wide screen in a big family with migraine problem. Additionally fine-mapping of several SNP markers limited the disease critical region to 8.5 Mb. We sequenced 9 candidate genes , unveiling no disease-associated polymorphisms in CLIC5, PLA2G7, SLC29A1, IL17, SLC25A27 and TNFRSF21. EFHC1 has recently been proven to be linked to epilepsy, which is certainly fascinating considering the link between migraine and epilepsy. Nevertheless, association analysis of EFHC1 uncovered no distinction among sufferers and controls, suggesting that this gene isn’t a risk factor for migraine. The combo of the 2 polymorphisms in RHAG and MEP1A could, still, not be present in any control individuals, suggesting that they could possibly be linked to genetic predisposition to migraine within this family. Conditions with decreased pain sensitivity are rare, because pain perception is important for survival. Several disorders have however been recognized with pain insensitivity and peripheral nerve degeneration as significant clinical indicators, such as the hereditary sensory and autonomic neuropathies (HSAN). To be able to discover novel susceptibility genes for HSAN V, we carried out a genome-wide screen in a huge consanguineous pedigree from the small village. Analysis of candidate genes exposed a missense mutation inside a conserved region of the nerve growth factor beta (NGFB) gene, resulting in a severe amino acid change (R211W) in the NGF protein. NGF is crucial for the development and upkeep of the sympathetic and sensory nervous system and is for that reason gonna be associated with disease.
What is migraine?
Contents
AIMS OF THIS THESIS
BACKGROUND
Why study pain?
What is pain?
Is pain heritable?
INTRODUCTION
Migraine
Genetic epidemiology
Prevalence
Gender and age
Ethnicity
Types of migraine
Migraine without aura (MO)
Migraine with aura (MA)
Familial hemiplegic migraine (FHM)
Relationship between MA and MO
Heritability of migraine
Family studies
Twin studies
Susceptibility genes and risk factors
Susceptibility genes in familial hemiplegic migraine
Susceptibility loci in common forms of migraine
Linkage studies of candidate FHM loci
Linkage studies of other candidate regions
Genome-wide screens of common migraine
Candidate gene association studies
Environmental risk factors
Mechanism of disease
Migraine models in mice
Pain insensitivity
Types of HSAN
HSAN I
HSAN II
HSAN III
HSAN IV
HSAN V
The NGF-TrkA system
Family of neurotrophins
Neurotrophin signaling
Neurotrophin processing
NGF mice models
Neurotrophins in human disease
METHODOLOGY
Patient material
Migraine
Pain insensitivity
Genealogical studies
Molecular genetic methods
Genome-wide scan
Candidate gene analysis
Genetic markers
Microsatellite markers
Single nucleotide polymorphisms ……
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Source: Umea University