The new genomics: Global views of biology

Science

Volumn 274, Issue 5287, 1996, Pages 536-539

  Lander, Eric S ^a  

^a WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; RNA;

DNA DETERMINATION; GENE MAPPING; GENETIC VARIABILITY; HUMAN GENETICS; MEDICAL ETHICS; MOLECULAR BIOLOGY; PRIORITY JOURNAL; PROTEIN MODIFICATION; PUBLIC OPINION; REVIEW; RNA ANALYSIS; SEQUENCE ANALYSIS; SEQUENCE HOMOLOGY;

ANIMALS; BIOETHICS; DNA; GENE EXPRESSION; GENETIC TECHNIQUES; HUMAN GENOME PROJECT; HUMANS; MICE; MOLECULAR BIOLOGY; PROTEINS; RNA; SEQUENCE ANALYSIS, DNA; VARIATION (GENETICS);

EID: 0029805706     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.274.5287.536     Document Type: Review

References (20)

1. T. J. Hudson et al., Science 270, 1945 (1995); C. Dib et al., Nature 380, 152 (1996); G. Shuler et al., Science 274, 540 (1996).
2. T. J. Hudson et al., Science 270, 1945 (1995); C. Dib et al., Nature 380, 152 (1996); G. Shuler et al., Science 274, 540 (1996).
3. T. J. Hudson et al., Science 270, 1945 (1995); C. Dib et al., Nature 380, 152 (1996); G. Shuler et al., Science 274, 540 (1996).
4. Because sites of human polymorphism occur roughly every kilobase, it will not suffice to compare a single affected individual and a single unaffected individual. However, comparison of many individuals will likely implicate the correct gene as having a high proportion of variants in affecteds.
5. M. Chee et al., Science 274, 610 (1996).
6. Although systematic data are limited, it is common experience to find no differences in coding sequence between two random individuals, which indicates a small effective number of alleles.
7. 6, Although only approximate, the model clearly indicates that n is small.
8. Given the limited information about population variation, I am deliberately vague about the precise populations to study. Studies of coding variation in a few dozen genes in several large populations would provide an adequate answer.
9. See, for example, E. S. Lander and N. J. Schork, Science 265, 2037 (1994).
10. 2 = 7.3.
11. The use of genetic markers to recognize chromosomes descended from a common ancestral haplotype, called linkage disequilibrium mapping, is a powerful method for fine-structure mapping of Mendelian traits in isolated populations, such as in Finland [J. Hastbacka et al,. Cell 78, 1073 (1994)]. With a sufficiently dense genetic map, ancestral haplotypes should be detectable in larger and older populations. For example, an ancestral mutation introduced into a population 1000 generations ago (≈20,000 years) wilt reside in a region of about 0.2 cM (or about 200 kb) in which recombination has not altered the ancestral haplotype. The density of polymorphism should permit unique recognition of such a region.
12. P. W. Holland et al., Development, suppl. 125 (1994).
13. Efficient approaches will be needed to rapidly isolate orthologous genes from a collection of organisms, at least until sequencing of entire genomes becomes routine.
14. M. Schena, D. Shalon, R. W. Davis, P. O. Brown, Science 270, 467 (1995); D. Lockhart et al., Nature Biotech., in press.
15. M. Schena, D. Shalon, R. W. Davis, P. O. Brown, Science 270, 467 (1995); D. Lockhart et al., Nature Biotech., in press.
16. H. H. McAdams and L. Shapiro, Science 269, 650 (1995).
17. P. L. Bartel et al., Nature Genet. 12, 72 (1996).
18. L. Holm and C. Sander, Science 273, 595 (1996).
19. N. Risch and K. Merikangas, ibid., p. 1516.
20. I thank D. Botstein, M. Chee, F. Collins, G. Duyk, E. Harlow, I. Herskowitz, R. Klausner, D. Lockhart, D. Mack, D. Page, R. Tepper, R. Weinberg, and other colleagues for valuable discussion and comments.