Genes/Expressions/Hair colors

Hominins generally have head, facial, and body hair of one or more colors or white hair.

The objective of this learning project is to determine gene suites that may be contributing to or causing white hair, failing to remedy white hair, or failing to maintain a hair color, or colors, other than white.

Under, or over expression, of genes in each suite may alter gene expression sufficiently to add to adverse effects.

Altered expression of genes from each suite may reduce or remedy white hair.

Gene expressions
Gene expressions is a suite of genes, and their isoforms, that appear to be biochemically involved in the appearance of a hair color or white hair.

A concept search of the National Institutes of Health NCBI gene database (http://www.ncbi.nlm.nih.gov/gene/) may provide possible initial genes (and associated isoforms and variants) participating in or causing white hair, failing to remedy white hair, or failing to maintain a hair color, or colors, other than white.

Gene IDs
"The minimum set of data necessary for a gene record, therefore, is: a unique identifier, or GeneID, assigned by NCBI; a preferred symbol; and either defining sequence information, map information, or official nomenclature from an authority list."

"A unique GeneID is assigned to each new record. There are currently two number generators being used by Gene; one that is assigning values in the range of 7,000,000 – 99,999,999 and another that is assigning values > 100,000,000. Thus the sequence of GeneIDs is expected to have gaps."


 * 1) Gene ID: 351 APP, amyloid beta precursor protein.
 * 2) Gene ID: 434 ASIP, agouti signaling protein.
 * 3) Gene ID: 1029 CDKN2A, cyclin-dependent kinase inhibitor 2A.
 * 4) Gene ID: 1385 CREB1, cAMP responsive element binding protein 1.
 * 5) Gene ID: 1392 CRH, corticotropin releasing hormone.
 * 6) Gene ID: 1393 CRHBP, corticotropin releasing hormone binding protein.
 * 7) Gene ID: 1394 CRHR1, corticotropin releasing hormone receptor 1.
 * 8) Gene ID: 1395 CRHR2, corticotropin releasing hormone receptor 2.
 * 9) Gene ID: 1638 DCT, dopachrome tautomerase.
 * 10) Gene ID: 1652 DDT, D-dopachrome tautomerase.
 * 11) Gene ID: 2247 FGF2, fibroblast growth factor 2.
 * 12) Gene ID: 2847 MCHR1, melanin concentrating hormone receptor 1.
 * 13) Gene ID: 3056 HCL1, hair color 1 (brown).
 * 14) Gene ID: 3057 HCL2, hair color 2 (red).
 * 15) Gene ID: 3257 HPS1, biogenesis of lysosomal organelles complex 3 subunit 1.
 * 16) Gene ID: 3309 HSPA5, heat shock protein family A (Hsp70) member 5.
 * 17) Gene ID: 3320 HSP90AA1, heat shock protein 90kDa alpha family class A member 1.
 * 18) Gene ID: 3662 IRF4, interferon regulatory factor 4.
 * 19) Gene ID: 3688 ITGB1, integrin subunit beta 1.
 * 20) Gene ID: 3690 ITGB3, integrin subunit beta 3.
 * 21) Gene ID: 3815 KIT, KIT proto-oncogene receptor tyrosine kinase.
 * 22) Gene ID: 4157 MC1R, melanocortin 1 receptor.
 * 23) Gene ID: 4158 MC2R, melanocortin 2 receptor.
 * 24) Gene ID: 4159 MC3R, melanocortin 3 receptor.
 * 25) Gene ID: 4160 MC4R, melanocortin 4 receptor.
 * 26) Gene ID: 4161 MC5R, melanocortin 5 receptor.
 * 27) Gene ID: 4254 KITLG, KIT ligand.
 * 28) Gene ID: 4286 MITF, melanogenesis associated transcription factor.
 * 29) Gene ID: 4935 GPR143, G protein-coupled receptor 143.
 * 30) Gene ID: 4948 OCA2, HCL3, OCA2 melanosomal transmembrane protein.
 * 31) Gene ID: 5077 PAX3, paired box 3.
 * 32) Gene ID: 5367 PMCH, pro-melanin concentrating hormone.
 * 33) Gene ID: 5369 PMCHL1, pro-melanin concentrating hormone like 1 (pseudogene).
 * 34) Gene ID: 5370 PMCHL2, pro-melanin concentrating hormone like 2 (pseudogene).
 * 35) Gene ID: 5443 POMC, proopiomelanocortin, melanocyte-stimulating hormone (MSH).
 * 36) Gene ID: 5879 RAC1, ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1).
 * 37) Gene ID: 5925 RB1, RB transcriptional corepressor 1, Rb interacts with the TYR promoter.
 * 38) Gene ID: 6490 PMEL, premelanosome protein.
 * 39) Gene ID: 6509 SLC1A4, solute carrier family 1 member 4.
 * 40) Gene ID: 6663 SOX10, SRY-box 10.
 * 41) Gene ID: 7037 TFRC, transferrin receptor.
 * 42) Gene ID: 7040 TGFB1, transforming growth factor beta 1.
 * 43) Gene ID: 7299 TYR, tyrosinase.
 * 44) Gene ID: 7306 TYRP1, tyrosinase related protein 1.
 * 45) Gene ID: 8490 PMEL, premelanosome protein.
 * 46) Gene ID: 8546 AP3B1, adaptor related protein complex 3 beta 1 subunit.
 * 47) Gene ID: 8558 CDK10, cyclin-dependent kinase 10.
 * 48) Gene ID: 8924 HERC2, HECT and RLD domain containing E3 ubiquitin protein ligase 2.
 * 49) Gene ID: 11234 HPS5, biogenesis of lysosomal organelles complex 2 subunit 2.
 * 50) Gene ID: 23166 STAB1, stabilin 1.
 * 51) Gene ID: 26258 BLOC1S6, biogenesis of lysosomal organelles complex 1 subunit 6.
 * 52) Gene ID: 51151 SLC45A2, solute carrier family 45 member 2.
 * 53) Gene ID: 51176 LEF1, lymphoid enhancer binding factor 1.
 * 54) Gene ID: 55576 STAB2, stabilin 2.
 * 55) Gene ID: 55770 EXOC2, exocyst complex component 2.
 * 56) Gene ID: 79083 MLPH, melanophilin.
 * 57) Gene ID: 79803 HPS6, biogenesis of lysosomal organelles complex 2 subunit 3.
 * 58) Gene ID: 84062 DTNBP1, dystrobrevin binding protein 1.
 * 59) Gene ID: 84343 HPS3, biogenesis of lysosomal organelles complex 2 subunit 1.
 * 60) Gene ID: 84447 SYVN1, synoviolin 1, interacts with TYR.
 * 61) Gene ID: 84539 MCHR2, melanin concentrating hormone receptor 2
 * 62) Gene ID: 89781 HPS4, biogenesis of lysosomal organelles complex 3 subunit 2.
 * 63) Gene ID: 123041 SLC24A4, solute carrier family 24 member 4.
 * 64) Gene ID: 219931 TPCN2, two pore segment channel 2.
 * 65) Gene ID: 340273 ABCB5, ATP binding cassette subfamily B member 5.
 * 66) Gene ID: 388552 BLOC1S3, biogenesis of lysosomal organelles complex 1 subunit 3.
 * 67) Gene ID: 100037417 DDTL, D-dopachrome tautomerase like.

Gene clusters
GeneID: 348 APOE apolipoprotein E description also contains this: "This gene maps to chromosome 19 in a cluster with the related apolipoprotein C1 and C2 genes."

Although these genes on chromosome 19 may not be expressed when APOE is expressed, they may be close enough or part of the cluster that is activated. Each of these would then be checked against the NASA database and the open literature searchable with Google Scholar or other search engines.

Gene regulations
Each gene, or its isoforms, is likely to have upregulation and downregulation transcription factors. As each gene is investigated, these enhancers and inhibitors are noted as discovered.

Gene similarities
There are genes on other chromosomes that are similar to each gene being considered. For example, GeneID: 338, Apolipoprotein B, is on chromosome 2. Yet it has been included in studies of rat models for predicting skeletal changes during spaceflight.

Human DNA
"[H]uman DNA has millions of on-off switches and complex networks that control the genes' activities. ... [A]t least 80% of the human genome is active, which opposed the previously held idea that most of the DNA are useless." By Bryan McBournie (September 6, 2012) "Human genome study could unlock the biology of disease", American Scientist.

"DNA contains genes, which hold the instructions for [life. But, these] take up only about 2 percent of the genome ... The human genome is made up of about 3 billion “letters” along strands that make up the familiar double helix structure of DNA. Particular sequences of these letters form genes, which tell cells how to make proteins. People have about 20,000 genes, but the vast majority of DNA lies outside of genes. ... [A]t least three-quarters of the genome is involved in making RNA [...] it appears to help regulate gene activity." By Malcolm Ritter (September 6, 2012) "Far from being mostly junk, human DNA is ‘a jungle’ of complex activity, huge project shows", The Washington Post.

There are "more than 4 million sites where proteins bind to DNA to regulate genetic function, sort of like a switch." Ritter, ibid.

Over 50% of human DNA consists of non-coding repetitive sequences, from T. Wolfsberg, J. McEntyre, and G. Schuler "Guide to the draft human genome" Nature 409 (6822) 824–6 (2001).

Some DNA sequences may encode functional non-coding RNA molecules, which are involved in the regulation of gene expression, from The ENCODE Project Consortium, "Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project", Nature 447 (7146) 799–816 (2007).

About 2700 formerly active genes are now pseudogenes. Additional DNA is used in introns and for centromeres and telomeres.

Some introns themselves encode specific proteins or can be further processed after splicing to generate noncoding RNA molecules, by D. Rearick, A. Prakash, A. McSweeny, S.S. Shepard, L. Fedorova, and A. Fedorov, "Critical association of ncRNA with introns", Nucleic Acids Research 39 (6) 2357–66 (March 2011).

Epigenomes
Inside each eukaryote nucleus is genetic material (DNA) surrounded by protective and regulatory proteins. These protective and regulatory proteins and the dynamic changes to them that occur during the course of a eukaryote's existence are the epigenome.

There are "nearly 50,000 acetylated sites [punctate sites of modified histones] in the human genome that correlate with active transcription start sites and CpG islands and tend to cluster within gene-rich loci." by Bradley E. Bernstein, Alexander Meissner, and Eric S. Lander, "The Mammalian Epigenome", Cell, (February 23, 2007) 128 (4) 669–81.

Any of the epigenome sites may be influenced during or before transcription to modify gene expressions.

Gene transcriptions
Gene transcription involves gene promoters that may lie upstream of the gene or downstream. The number and variety of gene promoters, enhancers and inhibitors, and other triggers for each gene can by quite large, but each may be an opportunity to alter gene expression as needed.

There are at least 60 specific transcription factors, such as the TATA box, that initiate or contribute to transcription.

Hypotheses

 * 1) The transcription of each gene, or its isoforms, is an opportunity to influence under or over expression.
 * 2) Like simvastatin, the product of some genes that may produce harmful effects can be muted by a biochemical that uses up some of the gene product before it produces unhealthy levels of that product.
 * 3) Gene expressions can be altered such as with the birth control pill that alters the apparent hormone balance to appear as if the woman is pregnant so as to prevent pregnancy.

"Black-haired individuals were only encountered in the control group, whereas light blond and red hair color were overrepresented in the melanoma group. The distribution of the different eye colors (brown, gray, green, and blue) was not different between the melanoma patients".