Confirmation that Xq27 and Xq28 are susceptibility loci for migraine in independent pedigrees
and a case-control cohort
Maher B.H.1, Kerr M.1, Cox, H.C.1, MacMillan J.C.2, Brimage P.J.3, Esposito T.4, Gianfrancesco F.4,
Haupt L.M.1, Nyholt D.5, Lea, R.A.1, Griffiths L.R.1
1
Genomics Research Centre, School of Medical Science, Griffith Health Institute, Griffith University,
Gold Coast, Queensland, Australia, 2 Queensland Clinical Genetics Service, Royal Children's Hospital,
Herston, Brisbane, Australia,
3
Institute of Neurological Sciences, Prince of Wales Hospital, New South Wales, Australia
4
Institute of Genetics and Biophysics, Italian National Research Council, Naples, Italy
5
Neurogenetics Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland,
Australia,
Corresponding author:
Professor Lyn Griffiths
e-mail: l.griffths@griffth.edu.au
Genomics Research Centre, Griffith Health Institute,
Griffith University, Queensland 4222, Australia.
t: +61 7 5552 8664
f: +61 7 5552 9081
Marker
Primers
Amplicon
DXS8064
F: FAM - AGAATCGCTTGACCCTTG 3’
R:CTGATGGCTGCCAACTC 3’
208-214bp
DXS1001
F: FAM - TGTACAAGTAACCCTCGTGACACG 3’
R: TAGTGGCTGGCAGAGAGATTCC 3’
376-386bp
DXS1206
F: FAM - TGCCATAGGTAGTCATAGCATAGCC 3’
R: CAGAGCATGGGACTTCTCAACC 3’
277-291bp
DXS984
F: NED - TGGAGGTCTGATTTAATGGCAGC 3’
R: GCCCTACTCCATTCCACACTGG 3’
127-141bp
DXS8106
F: FAM - CTCCTTGCACTTGCTGTGG 3’
R: TGCTTGCACCCTGTGAAGTC 3’
387-405bp
DXS8043
F: FAM - AGTTCTCAGAAACATTTGGTTAGGC 3’
R: AATTATTGGCAAAGAGTACAGGCAG 3’
166-184bp
DXS297
F: NED - TTGGACTTCCCAAGCCTCCACAA 3'
R: TTCTGAGTCTGTGCAGTGTATTTGTCAG 3'
191-197bp
DXS8091
F: FAM - CCACATTCAGGTTCCACAGGTACC 3’
R: TGCAAGATCCAGGCAAAAGTCTC 3’
90-108bp
DXS1123
F: FAM - TGCCTAAATGTTCGCAAGCCCATTC 3’
R: ACAAACAGCTGCCTCCTAGAAACCC 3’
168-176bp
DXS8061
F: VIC - GCAAGCTTGAAGTGTCCATGAGG 3’
R: AGAAGCTGATGTGCTCCCTGC 3’
141-155bp
DXS15
F: PET - AGCACATGGTATAATGAACCTCCACG 3'
R: CAGTGTGAGTAGCATGCTAGCATTTG 3'
154-166bp
DXS1073
F: VIC - TTGGGTGGAATTCCGTGACC 3’
R: CCAAAGAATGCCCTCTCCGA 3’
197-211pb
DXS1108
F: PET - GGAGTGAATTCATCATATGTGATTTCC 3’
R: ACTAGGCGACTAATACAGTGGTGCTC 3’
168-184bp
GPR50
F: VIC - GCCTGACTCTGTTCATTTCAAGCCT
R: CTTAGGGTGGCTGGTAGTGGCA
196-208bp
Online Resource 1: Primer Sequences and Labels
Xq27 Candidate Genes
SLITRK2
CXorf1
Gene
Product
SLIT and NTRK-like family, member 2
chromosome X open reading frame 1
Gene
GRP50
Product
Orphan G-protein coupled receptor 50
CNGA2
Cyclic nucleotide gated ion channel
GABRA3
NSDHL
ATP2B3
ABCD1
Gamma-aminobutyric acid (GABA) A receptor, alpha 3
NAD(P) Dependant Steroid Dehydrogenase-like
ATPase Ca2+ transporting plasma membrane 3
(PMCA3)
ATP-binding cassette, sub-family D (ALD), member 1
FLNA
filamin A, alpha (actin binding protein 280)
GDI1
GDP dissociation inhibitor 1
CLIC2
Chloride Intracellular Channel 2
Function
May play a role in modulating nuerite activity
Exact function is unknown however is expressed in the hippocampus
# SNPs analysed
2
2
Xq28 Candidate Genes
Online Resource 2: Xq27 and Xq28 Candidate Genes
Function
Expressed in the hypothalamus and the pituitary and has shown positive
association between bipolar affective disorder and major depressive
disorder in women.
Expressed in the middle cerebral and basilar arteries and the trigeminal
ganglion. Rat studies have shown that cyclic nucleotide gated channels
affect membrane potential suggesting that they may have a role in
regulating excitability in the CNS.
GABA, the major inhibitory neurotransmitter in the vertebrate brain
Involved in cholesterol biosynthesis
Brain specific receptor that potentially has a role in calcium homeostasis
and signalling.
Involved in peroxisomal import of fatty acids and/or fatty acyl-CoAs in
the organelle
This actin-binding protein interacts with integrins, transmembrane
receptor complexes, and second messengers
Primarily expressed in neural and sensory tissues, GDI1 Regulates the
GDP/GTP exchange reaction of most Rab proteins
Voltage-gated chloride channel activity, that may modulate Ryanodine
Receptor (RyR) calcium release channels
# SNPs analysed
1
3
10
6
5
1
1
1
2