Methods and compositions for inhibiting and treating neurological conditions

1. A method of hybridizing a nucleic acid probe or synthesizing a nucleic acid product from a sample from a human subject with parkinsonism, the method comprising:

(a) hybridizing a nucleic acid probe to a polynucleic acid from the sample by nucleic acid hybridization or microarray analysis, or

synthesizing a nucleic acid product from a polynucleic acid from the sample by PCR or sequencing; and

(b) detecting a genetic variation from the human subject by the nucleic acid hybridization, microarray analysis, PCR or sequencing,

wherein the genetic variation is a copy number variation (CNV) comprising a deletion of SEQ ID NO.: 18 or the complement thereof, a CNV comprising a deletion of SEQ ID NO.: 19 or the complement thereof, or a CNV that is a deletion of SEQ ID NO.: 18 having the 3′ terminal 12,860 nucleotides of SEQ ID NO.:18 or the complement thereof,

wherein the genetic variation is in a UNC13C gene (gene number 258).

2. The method of claim 1 , wherein the genetic variation disrupts or modulates a RNA transcript with a sequence of SEQ ID NO.: 206, or a protein product encoded by the RNA transcript.

3. The method of claim 1 , wherein the genetic variation comprises a CNV comprising a deletion of SEQ ID NO: 19 or the complement thereof.

4. The method of claim 1 , wherein the genetic variation comprises a CNV that is a deletion the 3′ terminal 12, 860 nucleotides of SEQ ID NO.: 18 or the complement thereof.

5. The method of claim 1 , wherein the genetic variation results in a loss of function of the UNC13C gene.

6. The method of claim 1 , wherein a whole genome or exome of the human subject is analyzed.

7. The method of claim 1 , wherein the sample is blood, saliva, urine, serum, tears, skin, tissue or hair from the human subject.

8. The method of claim 1 , wherein the detecting comprises purifying or amplifying polynucleotides from the polynucleic acid; and performing a microarray analysis of the purified or amplified polynucleotides.

9. The method of claim 1 , wherein the microarray analysis is an array Comparative Genomic Hybridization (CGH) analysis.

10. The method of claim 1 , wherein the sequencing is high-throughput sequencing.

11. The method of claim 1 , wherein the detecting comprises detecting a first genetic variation that is the CNV comprising a deletion of SEQ ID NO: 18 or the complement thereof, the CNV comprising a deletion of SEQ ID NO: 19 or the complement thereof, or the CNV that is a deletion of the 3′ terminal 12, 860 nucleotides of SEQ ID NO.: 18 or the complement thereof, wherein the first genetic variation and a second genetic variation are in a panel comprising two or more genetic variations.

12. The method of claim 11 , wherein the detecting comprises detecting at least two of the two or more genetic variations.

13. The method of claim 12 , wherein the two or more genetic variations of the panel comprise 10 or more genetic variations.

14. The method of claim 1 , wherein the parkinsonism is Parkinson's Disease (PD).

15. A method comprising administering a therapeutic agent that treats or slows the progression of one or more symptoms of parkinsonism to a human subject with parkinsonism, wherein the human subject comprises a genetic variation, wherein the genetic variation is a copy number variation (CNV) comprising a deletion of SEQ ID NO.: 18, a CNV comprising a deletion of SEQ ID NO.: 19 or the complement thereof, or a CNV that is a deletion of the 3′ terminal 12,860 nucleotides of SEQ ID NO.: 18 or the complement thereof, wherein the genetic variation is in a UNC13C gene (gene number 258), and wherein a sample from the human subject has been assayed to detect the presence of the genetic variation.

16. The method of claim 1 , wherein the genetic variation comprises a CNV comprising a deletion of SEQ ID NO.: 18 or the complement thereof.

17. The method of claim 11 , wherein the second genetic variation is intergenic.