Human genomics/Attributions

2011-08-30T06:25:25Z

Kathleen:

Kathleen:

[[Image:HumanGenomicsCover1.jpg|right|318x450px|HumanGenomicsCover1.jpg]]

== Human genomics: from hypothetical genes to biodigital materialisations ==

Edited by Kate O'Riordan

 

== Contents ==

==== Introduction ====

 

==== Section: 1 - Biodigital life: mobilising individual genomes in genomic research ====

In this article the direct-to-consumer genetics company, 23andMe, publish their results from self-reporting or crowd sourced samples. These participant driven studies potentially open up consumer derived genetic databases and self reported phenotypical information to biomedical research.

*[http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000993 Eriksson N, Macpherson JM, Tung JY, Hon LS, Naughton B, et al. 2010 Web-Based, Participant-Driven Studies Yield Novel Genetic Associations for Common Traits. PLoS Genet 6(6): e1000993.]

Author Summary

Twin studies have shown that many human physical characteristics, such as hair curl, earlobe shape, and pigmentation are at least partly heritable. In order to identify the genes involved in such traits, we administered Web-based surveys to the customer base of 23andMe, a personal genetics company. Upon completion of surveys, participants were able to see how their answers compared to those of other customers. Our examination of 22 different common traits in nearly 10,000 participants revealed associations among several single-nucleotide polymorphisms (SNPs, a type of common DNA sequence variation) and freckling, hair curl, asparagus anosmia (the inability to detect certain urinary metabolites produced after eating asparagus), and photic sneeze reflex (the tendency to sneeze when entering bright light). Additionally our analysis verified the association of a large number of previously identified genes with variation in hair color, eye color, and freckling. Our analysis not only identified new genetic associations, but also showed that our novel way of doing research—collecting self-reported data over the Web from involved participants who also receive interpretations of their genetic data—is a viable alternative to traditional methods. 

==== Section: 2 - Personal genomes: attempting clinical relevance. ====

So far personal genomics has not had much application in clinical contexts. The overwhelming amount of highly specialised data generated by whole genome sequencing, and the light touch probabilities of genome scanning present either too much, or too little information. This paper outlines an attempt to put personal genomics in a clinical context.

 

*[http://www.ncbi.nlm.nih.gov/pubmed/20435227 Ashley EA, Butte AJ, Wheeler MT, Chen R, Klein TE, Dewey FE, Dudley JT, Ormond KE, Pavlovic A, Morgan AA, Pushkarev D, Neff NF, Hudgins L, Gong L, Hodges LM, Berlin DS, Thorn CF, Sangkuhl K, Hebert JM, Woon M, Sagreiya H, Whaley R, Knowles JW, Chou MF, Thakuria JV, Rosenbaum AM, Zaranek AW, Church GM, Greely HT, Quake SR, Altman RB (2010) Clinical assessment incorporating a personal genome. Lancet 375: 1525-35. PMID: 20435227]

==== Section: 3 - Bioinformatic approaches    ====

Bioinformatics has become the dominant paradigm
for working with genomics in many areas. This does raise the question of who
can make sense of genomics – biologists or computer scientists. The exome paper below can been seen as one of the ways in which a debate about who is qualified to
make sense of genomics is playing out. Jenny Reardon’s (2011) paper available via subscription to ''Personalised''
Medicine'' ''(also available via Medscape) examines these tensions in the field
explicitly and gives a clear picture of some of the stakes.

*[http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000160 Genetic Variation in an Individual Human Exome]

Abstract: Characterizing the
functional variation in an individual is an important step towards the era of
personalized medicine. Protein-coding exons are thought to be especially
enriched in functional variation. In 2007, we published the genome sequence of J.
Craig Venter. Here we analyze the genetic variation of J. Craig Venter's exome,
focusing on variation in the coding portion of genes, which is thought to
contribute significantly to a person's physical make-up. We survey ~12,500
nonsilent coding variants and, by applying multiple bioinformatic approaches,
we reduce the number of potential phenotypic variants by ~8-fold. Our analysis
provides a snapshot of the current state of personalized genomics. We find that
<1% of variants are linked to any known phenotypes; this demonstrates the
dearth of scientific knowledge for phenotype-genotype associations. However,
~80% of an individual's nonsynonymous variants are commonly found in the human
population and, because phenotypic associations to common variants will be
elucidated via genome-wide association studies over the next few years, the
capability to interpret personalized genomes will expand and evolve. As
sequencing of individual genomes becomes more prevalent, the bioinformatic
approaches we present in this study can be used as a paradigm to pursue the
study of protein-coding variants for the genomes of many individuals.

 

==== Section: 4 - Genome Wide Association Studies (GWAS): from universal human genome to population variation. ====

==== ====

Haplotype mapping raises a whole set of debates and questions about race and human difference. This article sets out some of the later findings of the HapMap and demonstrates the kinds of typing that is going on in this area. For detailed accounts of the practices and challenges of this kind of human genomics see both Jenny Reardon’s ''Race to the Finish'' and Amade M’Charek’s ''The Human Genome Diversity Projec''t.

 

*[http://hapmap.ncbi.nlm.nih.gov/downloads/presentations/nature_hapmap3.pdf International HapMap Consortium. (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449(7164):851-861.]

==== 5) Publishing the reference genome from the Human Genome Project ====

The Human Genome Project ran from the late 1980s to 2003 and produced the human reference genome. These two articles signal the completion of the so-called first draft, which was announced to the world by the leaders of the USA and UK governments in 2000 (Roof, Nerlich). 

==== Section: 6 - Biochemistry, patents and genomics ====

In the early 1980s the technique called PCR – Polymerase Chain
Reaction was developed (see Rabinow for an anthropological account). Kary
Mullis won the Nobel Prize for his work in this area but his key article ‘An
unusual origin of PCR’ is not freely available and only accessible via
subscription.  However, a far more detailed and accessible article in the ''Journal of Biomedical Discovery and Collaboration ''(Fore, Weichers and Cook-Deegan 2006) is more useful at this point
and is included here. 

 This article examines the effect that the patent on PCR had on its
use in the sciences.  This is a useful piece because it provides a review of PCR in the genome sciences but also because it considers two key issues in genomics with particular relevance for the humanities. These are the related issues of commercial science and patenting.

The two issues are linked but not inseparable. Commercial companies and publicly funded research institutions both take out patents on inventions or discoveries.  PCR is a technique for reproducing large amounts of DNA and this facilitates sequencing. Kary Mullis’s work on this area was developed in a commercial setting.  Patenting and other commercial imperatives in the life sciences are part of the everyday reality of working in this area. Genomics is a 20th century science and has been developed within a highly commercialised system.

The most controversial dimensions of commercial practice in this
area is not the patent on PCR per se, but is around the question of the
patenting of genes and of genetic tests. 
This area is discussed further in relation to DNA in general in [http://www.nuffieldbioethics.org/patenting-dna The Ethics of Patenting DNA: A Discussion Paper] (2002, Nuffield Council on Bioethics).

 

*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1523369/ Fore, Joe Jr. Wiechers, lse R. and Cook-Deegan, Robert. 2006. The effects of business practices, licensing, and intellectual property on development and dissemination of the polymerase chain reaction: case study Journal of Biomedical Discovery and Collaboration 2006, 1:7doi:10.1186/1747-5333-1-7]

==== Section: 2 - Maps of life: catalogues, mapping and sequencing ====

===== a) maps =====

*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1686077/?tool=pubmed Botstein D, White RL, Skolnick M, Davis RW (1980) Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet. 32: 314-31] [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1686077/?tool=pubmed]

 

*[http://www.ornl.gov/sci/techresources/Human_Genome/project/herac2.shtml Subcommittee of the Health and Environmental Research Advisory Committee (HERAC). 1987. Report on the Human Genome Initiative, Office of Health and Environmental Research, Prepared for Dr. Alvin W. Trivelpiece Director, Office of Energy Research]

 

*[http://www.ornl.gov/sci/techresources/Human_Genome/publicat/OTAreport.pdf U.S. Congress, Office of Technology Assessment. 1988. Mapping Our Genes-The Genome Projects. How Big, How Fast? Washington, DC: U.S. Government Printing Office, April 1988]

 

===== b) catalogues   =====

In 1966 a medical field comes together through a catalogue and Dr Victor McKusick publishes the first print edition of Mendelian Inheritance in Man (MIM). This was an attempt to catalogue what was known about Mendelian phenotypes – or the physical expression of genetic material - as medically relevant characteristics. It later became Online Mendelian Inheritance in Man (OMIM). *[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2686440/ Amberger, Joanna. Bocchini, Carol A. Scott, Alan F. and Hamosh, Ada. McKusick's Online Mendelian Inheritance in Man (OMIM®) Nucleic Acids Res. 2009 January; 37(Database issue): D793–D796.]

==== Section: 1 - '''New''' genetics: scientific pictures and ordinary heroes ====

==== ====

The genetics of the 1950s helped to signal a break from the associations that had been made between human genetics and forms of social eugenics in the late 19th century and first half of the 20th century. This period of ‘discovery’ science also lead the way in providing narratives of scientific heroes as ordinary guys (McNeil). A version of scientific discovery that still resonates today as genetic heroics were reproduced by Craig Venter and John Sulston during the Human Genome Project, in biographies, autobiographies, popular science writing, news media and documentary.

In July 25, 1953 Rosalind Franklin and Gosling detail the distinctions between the A and B structures of the double helix in DNA and Watson and Crick publish their article on the structure of DNA.

*[http://www.nature.com/nature/dna50/franklingosling2.pdf Franklin R. and Gosling R.G. 1953. Evidence for 2-Chain Helix in Crystalline Structure of Sodium Deoxyribonucleate Nature 172, 156-157 (1953)]
*[http://www.nature.com/nature/dna50/watsoncrick.pdf Watson J.D. and Crick F.H.C. 1953. A Structure for Deoxyribose Nucleic Acid Nature 171, 737-738 (1953)]

 [http://www.livingbooksaboutlife.org/books/Human_genomics/Attributions Attributions]