73 Matching Annotations
  1. Dec 2017
    1. Affymetrix Genome-Wide Human SNP 6.0 Array

      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.

    2. Z. Arany et al., Nature 451, 1008 (2008).

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

    3. M. J. Percy et al., Proc. Natl. Acad. Sci. U.S.A. 103, 654 (2006).

      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.

    4. W. Zundel et al., Genes Dev. 14, 391 (2000).

      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.

    5. K. D. Pruitt, T. Tatusova, D. R. Maglott, Nucleic Acids Res. 33, D501 (2005).

      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.

    6. J. K. Pickrell et al., Genome Res. 19, 826 (2009).

      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.

    7. P. C. Sabeti et al., Nature 449, 913 (2007).

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

    8. E. P. Vargas, H. Spielvogel, High Alt. Med. Biol. 7, 138 (2006).

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

    9. O. M. Mejía, J. T. Prchal, F. León-Velarde, A. Hurtado,W. Stockton, Haematologica 90, 13 (2005).

      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.

    10. T. Wu et al., J. Appl. Physiol. 98, 598 (2005).

      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.

    11. C. M. Beall, Proc. Natl. Acad. Sci. U.S.A. 104, 8655 (2007).

      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.

    12. EGLN1 targets two HIFα proteins for degradation under normoxic conditions

      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.

    13. genome-wide regression analysis

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

    14. stepwise linear regression

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

    15. empirical significance level

      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.

    16. integrated haplotype score

      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.

    17. cross-population extended haplotype homozygosity (XP-EHH)

      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.

    18. Panther-defined pathway

      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.

    19. Gene Ontology

      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.

    20. priori functional candidate loci

      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.

    21. a genome-wide scan

      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

    22. priori candidates

      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.

    23. elevated circulating NO levels increase vasodilation and blood flow

      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.

    24. increased Hb concentration to compensate for the hypoxic high-altitude environmen

      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.

    25. Han Chinese

      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.

    26. and this response is associated with adverse effects


      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.

    27. lack of hypoxic pulmonary vasoconstriction

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

    28. decreased arterial oxygen content

      The levels of oxygen in the blood have fallen below normal

    29. Many present-day Tibetan populations are thought to be descendants of people who have occupied the Tibetan Plateau since the mid-Holocene, between 7000 and 5000 years ago


      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.

    30. Tibetan highlands

      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.

  2. Nov 2017
    1. phenotypes

      The observable characteristics/traits of organisms

    2. plausible

      An idea that is credible and reasonable

    3. tesaglitazar

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

    4. antidiabetic

      drugs used by diabetic patients to regulate blood glucose levels.

    5. normoxic

      Normal oxygen levels.

    6. heritable

      Able to be passed on to the next generation

    7. tabulated

      Data was arranged on a table or chart

    8. autosomal genes

      Are genes that are not on sex chromosomes

    9. localization signals

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

    10. 200-kb regions

      A measurement unit: 200 kilobytes

    11. intracellular calcium

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

    12. CAMK2D,

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

    13. HMOX2

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

    14. cytochrome P450 genes

      Family of genes that regulate lipid synthesis and drug metabolism.

    15. CYP2E1

      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.

    16. CYP17A1

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

    17. lipid metabolism pathway

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

    18. peroxisome proliferator–activated receptor (PPAR)

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

    19. subsequent

      Following a certain phenomenon

    20. nonoverlapping

      Structures that do not extend over one another

    21. consecutive

      A continuous uninterrupted sequence

    22. natural selection

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

    23. linkage disequilibrium

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

    24. partial selective sweeps

      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.

    25. point of fixation

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

    26. frequency

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

    27. haplotype

      A set of genes inherited by a single parent.

    28. single-nucleotide polymorphisms (SNPs)

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

    29. alleles

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

    30. resting ventilation

      resting breathing rate

    31. homeostasis

      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.

    32. transcriptional regulator

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

    33. positive selection

      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.

    34. ventilation

      The exchange of air between the lungs and atmospheric air.

    35. vasodilation

      The widening of blood vessels, which decreased blood pressure.

    36. NO

      Nitric oxide

    37. oxygen-transport system

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

    38. aerobic metabolism

      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.

    39. hypoxic

      low oxygen concentration

    40. compensate

      To make up for

    41. hemoglobin

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

    42. physiologic traits

      A characteristic associated with the normal function of the body.

    43. late Pleistocene

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