Genomic arrays are used to select for specific genes. In this study, a genomic array consisting of 1.8 million genetic markers including single nucleotide polymorphisms (SNPs) was used. The array displays genetic variation within SNPs. Affymetrix Genome-Wide Human SNP 6.0 Array was conducted to detect various markers such as SNPs to perform association studies, especially in larger samples. The array was conducted on 31 tibetan individuals to analyze alleles with a strong positive selection.

This paper explains how the transcriptional coactivator PGC-1alhpa regulates the transcription of VEGF necessary for angiogenesis.

This paper explains that the number of red blood cells is regulated by homeostatic mechanisms in the kidney. Low levels of oxygen results in anemia or low numbers of red blood cells, which induces erythropoietin production. As erythropoietin is produced, HIF is regulated which regulated genes for angiogenesis.

The loss of the PTEN gene activates the expression of HIF-1a. PTEN normally inhibits the response of Akt to hypoxic conditions. When not inhibited by PTEN Akt activates HIF-1a and HIF-1a is a transcription factors which aids in multiple mechanisms for tumor growth and progression (such as blood vessel formation). This paper discusses how the loss of PTEN is a mechanism tumors use to aid in progression by constitutively activating HIF-1a.

The National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) database provides a collection of sequences that represents transcripts and proteins, which are used for research.

This paper explains how genome-wide scans have been used to detect positive selection within a species, which gives great insight to the human population.

This paper explains how long-range haplotype methods can be used in correlation with genome wide scans to detect positive natural selection.

This paper explains how chronic mountain sickness associated with high altitudes is a major health issue.

Researchers conducted a study to exploit a possible population to determine the effects of erythropoietic responses and chronic mountain sickness. The results concluded that there was no associated polymorphisms linked to candidate genes.

This paper discusses the effect of gender on hemoglobin levels in Han Chinese and Tibetan Plateau inhabitants as a mechanism for high altitude adaptation. In Han populations a correlation was seen between increased altitude and increased hemoglobin levels (men having higher hemoglobin concentration than women), this correlation was not see in Tibetan highland inhabitants, or between genders of Tibetan highland individuals. The data suggests that the difference in hemoglobin concentrations between Han and Tibetan populations is dependent on gender.

This paper shows that the Tibetan and Andean populations have adapted to the high altitude through multiple physiological traits. Researchers assessed the basal and maximal oxygen consumption between the two populations and found that Tibetan and Andean populations had a higher oxygen consumption than low altitude populations. The results also revealed genetic variance in the Tibetan population, which suggested the potential for natural selection. Such genetic variance was higher in women as oxygen saturation of hemoglobin was higher.

Under normal oxygen levels, HIF proteins are degraded due to hydroxylation by a family of hydroxylases known as EGL- nine homologs (EGLN). As HIF is hydroxlyated, HIF is targeted by VHL proteins for degradation. Hydroxylation is the addition of a hydroxyl group. With HIF being degraded, transcription of genes needed for angiogenesis does not occur.

A regression in which the gene of interest is selected against genes that are not important to the study.

A method of regressing variables while removing those that aren’t important.

An empirical research is a research that uses observations that are verifiable rather than theories. The level of significance in an empirical research is the probability of rejecting the null hypothesis.

The measurement of the extended haplotype homozygosity (EHH) at a given SNP along the original allele relative to the derived allele. Like the cross population extended haplotype homozygosity, integrated haplotype score detects natural selection, even when the sample size is limited.

A comparison statistic test to determine the amount of homozygosity within two populations. Simonson et al., conducted a cross population extended haplotype homozygosity to compare the homozygosity between the Tibetan population, who live on highlands and Han Chinese (CHB) and Japanese (JPT), who live on lowlands. By comparing between the populations that live in different environments, alleles that have increased in frequency, sometimes upto fixation, can be pinpointed. Cross population extended haplotype homozygosity was used to identify six of the 10 genes that were selected from the 240 genes.

The HIF pathway is one of the molecular pathways used to regulate angiogenesis. The Hypoxia inducible factor (HIF) proteins act as transcription factors by inducing the vascular endothelial growth factor (VEGF) promoter. HIF proteins are activated as a result of low oxygen concentration. In normal conditions, the HIF protein is rapidly degraded by the actions of Von Hippel–Lindau (VHL) tumor suppressor proteins. VHL proteins bind to hydroxylated HIF and targets HIF for proteasomal degradation. However, under hypoxia, HIF is no longer bounded to oxygen and VHL can’t bind to HIF, resulting in the activation of HIF. HIF can then induce angiogenesis by activating VEGF genes.

Gene Ontology is an initiative that aims to address different concepts and vocabularies aimed to describe the functions of a gene and its products. Gene ontology studies genes based in three major categories: biological component, molecular functions and cellular compartments.

An approach focusing on associations between gene variations within the gene of interest and phenotypes. The loci is selected based on priori or independent knowledge of the gene’s function and impact. Based on the known functions of the genes, candidate loci were selected for additional studies such as genome-wide scanning. Gene Ontology project was conducted to select for a priori functional candidate loci. Various categories, such as detection of oxygen, NO metabolic process, oxygen sensor activity, oxygen binding, oxygen transport, response to hypoxia, response to oxygen levels and vasodilation were used to define a functional candidate loci.

An approach that scans markers of the entire set of DNA to find genetic variation associated with an adaptation or disease. Simonson et al., used genome-wide scan to identify genes that were positively selected for high altitude adaptations. By scanning through the entire set of DNA, genes were categorized into three groups: functional candidates, XP-EHH candidates and iHS candidates. The set of functional candidates consists of genes that are related to physiological traits of hypoxia. The XP-EHH and iHS consist of genes in in the top 1% of the sample

In genetics, candidate genes are genes that are likely to cause a disease due to their location or their protein products. Candidate genes are studies based on a priori knowledge. A priori knowledge is gained based on detective and derivative reasoning. Hence, a priori candidates are genes that cause disease and have been studied and analyzed.

Researchers have found that Tibetans have increased nitric oxide (NO) levels, which leads to an increase in vasodilation and blood flow. With higher NO levels causing an increase in blood flow, Tibetans have adapted to higher altitude levels.

When people have lived 2,500 meters above sea level, they experience hypoxia or lack of oxygen. In extreme cases of hypoxia people can experience altitude sickness. However, people who have lived at high altitudes for thousands of years have adapted to such extreme conditions. These people have an increased in hemoglobin concentration which compensates for hypoxia. With an increase in hemoglobin, oxygen is able to be transported through the body more efficiently.

Lorenzo VF, Yang Y, Simonson T, Nussenzveig R, Jorde LB, Prchal JT, Ge RL. Genetic adaptation to extreme hypoxia: study of high-altitude pulmonary edema in a three-generation Han Chinese family. Blood Cells Mol Dis. 2009 Nov-Dec; 43(3):221-5. PMID: 19481479; PMCID: PMC3506116.

The researchers isolated the genes responsible for high altitude pulmonary edema (HAPE) in a family of non-adapted Han Chinese, as to identify targeted treatment for HAPE. They discovered a HIF2A haplotype with all of the studied individuals with HAPE. Overall, a larger sample size was needed for more conclusive results. However, the data discovered can be analyzed to locate a region of the genome responsible for HAPE.

https://www.sciencedaily.com/releases/2017/09/170921161236.htm

Now that researchers have found that people are adapting to high altitudes, few have explored the adverse effects such as chronic mountain sickness. A research team of University of California is expanding their knowledge on both the adaptation and the adverse effects.

Normally, under hypoxic conditions, the blood vessels constrict. In Tibetans this physiologic reaction does not occur.

The levels of oxygen in the blood have fallen below normal

http://www.sciencemag.org/news/2014/07/tibetans-inherited-high-altitude-gene-ancient-human

According to news reports, Tibetans have inherited a "superathlete" gene that allows them to live in high altitudes. The gene has been acquired from interbreeding which has been shown to help humans in today's environment.

Landscape in Tibet where humans live, low levels of oxygen because of the altitude. The elevation is 4000-5000 meters with a total area of about 2 million km.

The observable characteristics/traits of organisms

An idea that is credible and reasonable

Is a drug that targets peroxisome proliferator-activated receptor. Peroxisome proliferator-activated receptor are nuclear receptors, which also act as transcription factors.

drugs used by diabetic patients to regulate blood glucose levels.

Normal oxygen levels.

Able to be passed on to the next generation

Data was arranged on a table or chart

Are genes that are not on sex chromosomes

Localization signals are amino acid sequences that aid in nuclear transport by tagging proteins destined into the nucleus.

A measurement unit: 200 kilobytes

Calcium found on the inside of the cell, typically found in the mitochondria.

CAMK2D gene encodes for calcium dependent protein kinase type 2 delta, which is a serine/threonine protein kinase family.

Heme oxygenase 2 (HMOX2) is an enzyme that catalyzes the breakdown of heme.

Family of genes that regulate lipid synthesis and drug metabolism.

Is one of the member of the cytochrome P450 superfamily, and regulates metabolism of xenobiotics in the body. Xenobiotics are chemical compounds found in the body, but are not synthesized within the body.

Cytochrome P450 17A1 is a gene encoding for enzymes of the cytochrome P450 superfamily, which regulate the synthesis of various lipids and drug metabolism.

The breakdown or storage of fats that occurs within cells, primary in the liver.

Peroxisome proliferator activated receptors are receptors found on the nuclear membrane that can act as transcription factors that induce certain genes.

Following a certain phenomenon

Structures that do not extend over one another

A continuous uninterrupted sequence

The evolutionary process in which organisms acquire adaptations to allow survival in an environment.

The phenomenon is which two or more alleles are associated more frequently than expected.

Beneficial mutations that increase an organism's survival and reproductive rate are favored by natural selection. That is, alleles that increase an individual’s fitness are increased in frequency. Eventually most beneficial mutations become fixed : their frequency will reach 1. However, mutations increase in frequency but don’t get fixed. Beneficial mutations that are nearly fixed result in partial selective sweep.

A change in the gene pool where one allele becomes the dominant allele.

The ratio of one allele to other alleles in a particular population.

A set of genes inherited by a single parent.

A DNA sequence variation that occurs in a single nucleotide base.

One or two alternate forms of a gene that have arisen via mutation, that are found at the same location on the same chromosome.

resting breathing rate

The tendency of a body toward balanced physiological conditions in reaction to specific stimulus. For example, maintaining a body temp of 98.6 F regardless of the environmental temperature.

A protein or molecule that regulates the transcription of DNA to RNA.

When a specific trait is made more prevalent overtime in a population (the Tibetan highlands people in this case), because this trait increases the survival and reproduction of the person who expresses it.

The exchange of air between the lungs and atmospheric air.

The widening of blood vessels, which decreased blood pressure.

Nitric oxide

The oxygen transport system consists of the lungs and blood vessels. Oxygen is transported from the lungs through blood vessels.

Cellular process where energy generated by the cell (in the form of ATP) is made through oxidative phosphorylation (the electron transport chain) where oxygen is the final electron acceptor.

low oxygen concentration

To make up for

A molecule found on red blood cells that is responsible for the transport of oxygen in the body of vertebrates.

A characteristic associated with the normal function of the body.

A time period between 2.6 million years ago to 11,700 years ago.