There are some other things in.
Gene candidates for germline genetic modification
Direct gene candidates
gobs of radiation resistance. prevent binding of thrombospondin to CD47 with a drug, inhibits NO production and somehow this prevents radiation damage and kills cancer cells. antisense CD47 RNA should do the trick permanently.
There are a number of options here, but with germline modification, a muscle-specific knockout of ACVR2B or myostatin are good choices. Also follistatin overexpression in muscle.
In muscle, this allows greatly improved metabolism and endurance (see 'mighty mice'). Synergistic effect with myostatin inhibition is untested, but intriguing.
As the "guardian of the genome", p53 is missing in many cancers, and has been investigated as a gene therapy option for cancer. Introducing a separate copy, or copies of the gene from the wild-type could reduce the incidence of knockout mutations that normally lead to cancer.
"Apolipoprotein A-1 Milano (also ETC-216, now MDCO-216) (ApoA-1 milano) is a naturally occurring mutated variant of the apolipoprotein A1 protein found in human HDL, the lipoprotein particle that carries cholesterol from tissues to the liver and is associated with protection against cardiovascular disease. ApoA1 Milano was first identified by Dr. Cesare Sirtori in Milan, who also demonstrated that its presence significantly reduced cardiovascular disease, even though it caused a reduction in HDL levels and an increase in triglyceride levels."
Humans are unsuited to digesting some types of branching carbohydrates, which then pass through the intestines and feed annoying bacteria. Not a huge priority, but with the increased metabolic demands from the muscle-enhancing therapies, it can't hurt.
Provides resistance to HIV and plague. Increases risk from West Nile virus, but who gives a fuck about that.
Also see HCP5 (rs2395029), and CCL3L1.
See also rs333 for other details.
LRP5 gene (strong bones)
Those with the LRP5 gene have extra strong bones.
PCSK5 (lower coronary disease)
Those with the PCSK5 gene have 88 percent lower coronary disease. Also, PCSK9 (according to George Church) is also capable of lowering susceptibility to coronary disease.
"More than 50 different mutations in the APP gene can cause early-onset Alzheimer disease, which begins before age 65."
FUT2 (norovirus / stomach flu resistance)
Those with double FUT2 are resistant to stomach flu.
Lactase persistence (lactose tolerance)
Also known as "C/T(-13910)", and located in the MCM6 gene but with influence on the lactase LCT gene, rs4988235 is one of two SNPs that is associated with the primary haplotype associated with hypolactasia, more commonly known as lactose intolerance in European Caucasian populations. [PMID 11788828], [PMID 15114531]
In these populations, the rs4988235(T) allele is both the more common allele and the one associated with lactase persistence; individuals who are rs4988235(C;C) are likely to be lactose intolerant. In populations of sub-Saharan Africans, though, the rs4988235(T) allele is so rare that it's unlikely to be predictive of lactase persistence, and other SNPs are predictive instead. [PMID 15106124, PMID 17159977]
Resistance to weight gain from high-fat diets (APOA5)
rs662799 increases risk of heart attack, but contributes towards preventing weight gain from high fat diets.
Hyperosmia (increased odor sensitivity)
rs1953558 - sensitivity to sweaty odor (isovaleric acid)
rs6591536 - detection of β-ionone (floral) fragrance
DARC - rs2814778
HBB - i3003137
G6PD - rs1050828
sweetness - TAS1R2
umami - TAS1R1
sourness - PKD2L1
spiciness - TRPV1
signal - GNAT3, TRPM5, PLCB2
bitterness - TAS2R4, TAS2R5, TAS2R16, TAS2R8, TAS2R38, TAS2R48
Sprinting vs. endurance
ACTN3 - rs1815739
green eye color - rs7495174
blue eye color - rs12913832
Modulated alcohol cravings
- genes implicated in learning include COMT, SLC6A3 (DAT1), DRD4, DRD2, PPP1R1B (DARPP32), MAOA, LMX1A, and BDNF
- FADS2 polymorphisms may modify the effect of breastfeeding on iq see rs1535
Variation in longevity gene KLOTHO is associated with greater cortical volumes see rs9536314 and the KL gene; related to the KL gene variants is rs9527025
AKT1 - rs1130214
- BDNF - rs6265
- BDNF - BDNF Val66Met allele is associated with reduced hippocampal volume in healthy subjects "The met-BDNF allele was associated with an 11% reduction in the volume of the hippocampal formation."
- CAMTA1 - rs4908449
- CLSTN2 - rs6439886 - associated with increased episodic memory performance
- COMT - rs4680
- CTSD - rs17571
- DAOA - rs3918342, rs1421292
- HTR2A - rs6314
- KIBRA / WWC1 - rs17070145, "Carriers of KIBRA rs17070145 T allele had 24% better free recall performance 5 min after word presentation (P = 0.000004) and 19% better free recall performance 24 hours after word presentation (P = 0.0008) than did noncarriers."
- NRG1 - rs35753505, rs6994992, SNP8NRG433E1006
- SorCS1 - rs10884402, rs7078098, rs950809, see Impact of genetic variation in SORCS1 on memory retention and The sorting receptor SorCS1 regulates trafficking of neurexin and AMPA receptors
- DTNBP1 - not rs2619522
- hippocampus volume - TESC - rs7294919, see Identification of common variants associated with human hippocampal and intracranial volumes
- intracranial volume - HMGA2 - rs10784502
- NRXN3 and other neurexins
- CTNNBL1 (beta-catenin-like protein 1)
- rs11074779 ??
- various dopamine D2 receptor changes
- APOE - alzheimers related? rs4420638 is associated with poorer delayed recall performance.
- SPOCK3 - (nearby?) rs6813517 - paragraph delayed recall - poor performance
- HS3ST4 - (nearby?) rs11074779 - paragraph delayed recall - poor performance
Some loci associated with hippocampal volume found in genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8), enzymes targeted by new diabetes medications (DPP4), and neuronal migration (ASTN2).
- DPP4 - rs6741949 - G allele, smaller hippocampus vlume
- ASTN2 - rs7852872 - C allele, smaller hippocampus volume
- rs7294919, located on 12q24 between HRK and FBXW8, T allele, smaller hippocampus volume
- rs17178006 - smaller hippocampus volume
- rs6581612, between WIF1 and LEMD3, smaller hippocampus volume
optimization of ubiquitin metabolism in hippocampus ? The deubiquitinating enzyme USP46 regulates AMPA receptor ubiquitination and trafficking. Also influences glutamate receptors.
- rs733722, near the choline acetyltransferase CHAT gene, -- controls whether galantamine can help fight mental decline in Alzheimer's disease
Exceptional episodic memory:
- MOXD1 (Monooxygenase, DBH-like 1) rs6902875 (when lacking an APOE ε4 allele); see also rs9321334 and rs4897574.
The polymorphisms rs1800497 and rs2283265 (also known as the Taq1a polymorphism) near the dopamine receptor 2 (DRD2) gene are associated with improvements during working memory training. However this polymorphism comes with serious tradeoffs: antisocial, borderline, dissocial, and avoidant personality disorders, addictive and impulsive behaviors such as binge eating, pathological gambling, and drug abuse. (more)
Other genes and polymorphisms associated with working memory improvements are listed on page 5 table 1: SLC6A3 (DAT1) rs27072 rs40184 rs3863145; DRD4 rs11246226 rs936465 rs7124601; PPP1R1B (DARPP32) rs3764352; MAOA rs6609257; ANKK1 rs1800497 (TAQ1A); DRD2 rs2283265; LMX1A rs4657412; BDNF rs6265; COMT rs4680
- Variants in SNAP25 are targets of natural selection and influence verbal performances in women
- DNA variation in the SNAP25 gene confers risk to ADHD and is associated with reduced expression in prefrontal cortex
Theoretical "heterozygote advantages" genes
The principle here is that diseases such as sickle cell or Tay-Sachs, among many others, persist in a population because having one 'good' and one 'bad' copy of the gene offers a significant advantage - in disease resistance, intelligence, etc.
While it would be nice to find a point mutation that would mimic the benefits of heterozygosity, the most straightforward option would be to give someone both variants of the gene, with ~50% expression of each.
- APOB rs1801703, rs12713450, rs12720854
- PPARGC1A rs148144750
- NRG1 rs62497784
- RAD52 rs35278212
- NCOR1 rs61753150
- RAD51 rs191297852
- ADCY5 rs61734561
Various frameshift indels in TET2 and DNMT3A, and high levels of granulocytes in blood. "Both TET2 and DNMT3A are factors [28,29] and are thought to silence hematopoietic stem cell self-renewal to permit efficient hematopoietic differentiation [30,31]. Therefore, loss of functionality in these genes is likely to underlie an enhanced self-renewal leading to the observed age-related myeloid lineage bias. This skewing towards the myeloid lineage is assumed to have adverse effects on immune functionality in normal healthy individuals, but in the oldest old the increase of the myeloid compartment might be compensative for the age-related decrease in naive T-cells, known as immuno-senescence. Hence on condition that the enhanced self-renewal, instigated by somatic disruptive mutations in TET2 and DNMT3A, leads to increased levels of competent immune cells, be it of the myeloid lineage though, might partly compensate for the age-related loss of immuno-capacity of the lymphoid compartment." (from "Germ line and somatic characteristics of the long-lived genome")
Maybe also mutations in:
- OBFC1 (telomere maintenance), rs77987791 rs77987791 rs7925084
- GSK3B (healthy aging index)
- NOTCH1 (diastolic blood pressure)
- TP53 (serum HDL)
- DCAF4 -- avoid rs2535913; keep G because A is associated with lower leukocyte telomere lengths.
Tetracycline response elements, i.e. tet-on and tet-off, can be used for transgenes where constant expression is undesirable. While a number of options for such inducible expression exist, the tet system is the most studied. It is left as an exercise to the reader to determine which genes would be suitable candidates [I will add some when I get around to it].
- rs4680 "worrier/warrior" cognitive effects
Candidate genes for sports doping
This is lifted from this table.
|Gene/product||System/organ targets||Gene product properties||Physiologic response|
|ACE||skeletal muscles||peptidyl dipeptidase||ACE-D is involved in fast twitch muscles.|
|ACTN3||skeletal muscles||actin-binding proteins related to dystrophin||Involved in fast-twitch muscles.|
|endorphins||central and peripheral nervous system||widely active peptides||pain modulation|
|EPO||hematopoietic system||glycoprotein hormone||Increases RBC mass and oxygen delivery.|
|HGH||endocrine system||191-amino acid protein||Increases muscle size, power, and recovery.|
|HIF||hematologic and immune systems||multisubunit protein||Regulates transcription at hypoxia response elements.|
|IGF-1||endocrine/metabolic/skeletal muscle||70-amino acid protein||Increases muscle size, power, and recovery by increasing regulator cells.|
|myostatin (MSTN)||skeletal muscle||2-subunit protein||Regulates skeletal muscle. Inhibition increases muscle size, power, and recovery.|
|PPAR-delta||skeletal muscle and adipose tissue||nuclear hormone receptor protein||Promotes fat metabolism and increases number of slow twitch fibers.|
|VEGF||vascular endothelium||glyosylated disulfide-bonded homodimers||Induces development of new blood vessels.|
Abbreviations: ACE, angiotensin-converting enzyme; ACTN3, actinin binding protein 3; EPO, erythropoetin; HGH, human growth factor; HIF, hypoxia inducible factor; IGF-1, insulin-like growth factor; PPAR-delta, peroxisome proliferators-activated receptor (delta); VEGF, vascular endothelial growth factor.
- alpha-actin-3 for endurance and increased power in sprinters
- myostatin and follistatin and muscle hypertrophy
- erythropoietin for red blood cell production
- insulin-like growth factor 1
- "an increase in synthesis of monoamines could improve the mood of athletes"
- preproenkephalin for pain reduction
- glucagon-like peptide 1 to increase glucose in liver and reduce lactic acid buildups for athletes
- endurance: ACE Alu I/D (rs4646994) (called ACE I); ACTN3 577X; PPARA rs4253778 G; PPARGC1A Gly482;
- power/strength markers: ACE Alu I/D (rs4646994) (called ACE D); ACTN3 Arg577; AMPD1 Gln12; HIF1A 582Ser; MTHFR rs1801131 C; NOS3 rs2070744 T; PPARG 12Ala;
- human tetrachromacy
- rs17822931 - dry earwax, sweat production, body odor
4-5 hours of sleep/night, plus resistance to sleep deprivation -- see http://gnusha.org/logs/2016-11-25.log
"The transcriptional repressor DEC2 regulates sleep length in mammals" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884988/ (hDEC2-P385R)
"A novel BHLHE41 variant is associated with short sleep and resistance to sleep deprivation in humans" https://go.aastweb.org/Resources/journalclub/journalcluboctober2014.pdf
- BHLHE41 - rs121912617
"Resisting sleep deprivation by breaking the link between sleep and circadian rhythms" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173912/
"TNFα G308A polymorphism is associated with resilience to sleep deprivation-induced psychomotor vigilance performance impairment in healthy young adults" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467999/
sleep duration - PAX8, VRK2 (vaccinia related kinase 2) (rs62158211, rs17190618, rs1380703), rs3768984
GNB3 - rs1047776 A allele and the rs2238114 C allele
ARNTL - rs10766071 "has been associated with shorter sleep duration"
ABCC9 - rs11046205 - A K(ATP) channel gene effect on sleep duration: from genome-wide association studies to function in Drosophila "rs11046205 explains ~5% of the variation in sleep duration. The A allele was associated with longer sleep duration, while the G allele was associated with shorter sleep duration"
ADA - rs73598374
CLOCK - rs12649507
FTO - rs9939609 - something about short sleep duration and weight gain in children?
SNP to re-enable human synthesis of vitamin C
dental caries vaccine
a genetically modified strain of Streptococcus mutans called BCS3-L1, is incapable of producing lactic acid, which dissolves tooth enamel, and aggressively replaces native flora. In laboratory tests, rats who were given BCS3-L1 were conferred with a lifetime of protection against S. mutans. Dr. Jeffrey D. Hillman suggests that treatment with BCS3-L1 in humans could also provide a lifetime of protection, or, at worst, require occasional re-applications. He figures the treatment would be available in dentists' offices and "will probably cost less than $100.
Cellular changes and molecular biology
Originally authored by yashgaroth on 2012-06-28. See http://gnusha.org/logs/2012-06-28.log for more context.