Background
Methods
General analysis strategy
Samples and SNP genotyping
Chip | France | Italy | USA | Netherlands | Total |
---|---|---|---|---|---|
Nsp
| 15 | 20 | 25 | 37 | 97 |
Sty
| 16 | 18 | 25 | 32 | 91 |
Nsp + Sty | 5 | 1 | 9 | 11 | 26 |
Total trios
| 26 | 37 | 41 | 58 |
162
|
Pathway-based analysis
Network analysis
ENCODE information for extra Genic SNPs
Results
Validation of the known HSCR-associated functionalities by PBA of the available chips from the different country populations
GO ID | Initial hypothesis | Italy | France | Netherlands | USA | |||||
---|---|---|---|---|---|---|---|---|---|---|
Nsp
|
Sty
|
Nsp
|
Sty
|
Nsp
|
Sty
|
Nsp
|
Sty
| |||
Signaling | GO:0051056 | Regulation of small GTPase mediated signal transduction | Y | Y | Y | Y | Y | |||
GO:0046578 | Regulation of Ras protein signal transduction | Y | Y* | Y | Y* | Y | ||||
GO:0007265
|
Ras protein signal transduction
|
Y
|
Y
|
Y
|
Y
|
Y
| ||||
GO:0007264
|
Small GTPase mediated signal transduction
|
Y*
|
Y*
|
Y*
|
Y*
| |||||
GO:0035023 | Regulation of Rho protein signal transduction | Y | Y | Y* | ||||||
GO:0009966
|
Regulation of signal transduction
|
Y*
|
Y*
|
Y*
|
Y
| |||||
GO:0007167
|
Enzyme linked receptor protein signaling pathway
|
Y
| ||||||||
GO:0007268
|
Synaptic transmission
|
Y
|
Y
|
Y
|
Y
| |||||
ENS formation |
GO:0006816
|
Calcium ion transport
|
Y
|
Y
|
Y*
|
Y*
|
Y*
| |||
GO:0006812
|
Cation transport
|
Y*
|
Y
|
Y*
|
Y
|
Y*
|
Y*
| |||
GO:0016337
|
Cell-cell adhesion
|
Y*
|
Y
|
Y
|
Y
|
Y
| ||||
GO:0016477
|
Cell migration
|
Y
|
Y
|
Y
| ||||||
GO:0007399
|
Nervous system development
|
Y
|
Y
|
Y
|
Y
| |||||
GO:0048666
|
Neuron development
|
Y
|
Y
|
Y
| ||||||
GO:0007409
|
Axonogenesis
|
Y
|
Y
|
Y
|
Comparison of the gene functionalities associated to HSCR observed between country sample populations
Network analysis
Extra-genic SNPs associated to HSCR that support the functionalities found
SNP | Nominal p-value | Adj. p-value (BH) | Chip | RefSeq genes | Feature | Proteins bound | Motifs changed |
---|---|---|---|---|---|---|---|
rs2435367 | 8.067×10-11 | 2.2083×10-06 |
Sty
| 5.9 kb 5′ of RET | DNAse hypersensitivity | ||
rs2505526 | 8.353×10-07 | 0.01506847 |
Sty
| 7.5 kb 3′ of RASGEF1A | Pax-4 | ||
rs16838932 | 4.459×10-07 | 0.021091873 |
Nsp
| 421 kb 5′ of SLC39A10 | Ultraconserved region [35] | ||
rs2659635 | 7.098×10-06 | 0,08204207 |
Sty
| 125 kb 5′ of XRCC6BP1 | Foxj2 | ||
rs4570660 | 7.744×10-06 | 0,08479448 |
Sty
| 65 kb 3′ of APOBEC1 | DNAse hypersensitivity | Sox | |
rs12067906 | 9.584×10-06 | 0,09994469 |
Sty
| 96 kb 5′ of RGS21 | DNAse hypersensitivity | RAD21 | Gfi1, HLF |