Article

Detection of potential GDF6 regulatory elements by multispecies sequence comparisons and identification of a skeletal joint enhancer.

Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Genomics (Impact Factor: 2.79). 10/2005; 86(3):295-305. DOI: 10.1016/j.ygeno.2005.05.003
Source: PubMed

ABSTRACT The identification of noncoding functional elements within vertebrate genomes, such as those that regulate gene expression, is a major challenge. Comparisons of orthologous sequences from multiple species are effective at detecting highly conserved regions and can reveal potential regulatory sequences. The GDF6 gene controls developmental patterning of skeletal joints and is associated with numerous, distant cis-acting regulatory elements. Using sequence data from 14 vertebrate species, we performed novel multispecies comparative analyses to detect highly conserved sequences flanking GDF6. The complementary tools WebMCS and ExactPlus identified a series of multispecies conserved sequences (MCSs). Of particular interest are MCSs within noncoding regions previously shown to contain GDF6 regulatory elements. A previously reported conserved sequence at -64 kb was also detected by both WebMCS and ExactPlus. Analysis of LacZ-reporter transgenic mice revealed that a 440-bp segment from this region contains an enhancer for Gdf6 expression in developing proximal limb joints. Several other MCSs represent candidate GDF6 regulatory elements; many of these are not conserved in fish or frog, but are strongly conserved in mammals.

Download full-text

Full-text

Available from: Arjun B Prasad, Jun 27, 2015
0 Followers
 · 
159 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The transcription of almost all developmental genes is driven by tissue- and time-specific regulatory elements. These transcriptional regulatory elements lie in the genomic DNA proximal to the gene, and hence are cis-regulatory (as opposed to trans-regulatory elements like transcription factor genes). Over the past three decades, a number of techniques have been applied to the problem of finding and characterizing these regulatory elements. In this chapter, I discuss some computational approaches that have been particularly useful in identifying developmental cis-regulatory regions, and provide a tutorial on how to apply these approaches to the study of chick development.
    Methods in cell biology 02/2008; 87:337-65. DOI:10.1016/S0091-679X(08)00218-5 · 1.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: This paper integrates in a unified and tractable framework some of the key insights of the field of international trade and economic growth. It examines a sequence of theoretical models that share a common description of technology and preferences but differ on their assumptions about trade frictions. By comparing the predictions of these models against each other, it is possible to identify a variety of channels through which trade affects the evolution of world income and its geographical distribution. By comparing the predictions of these models against the data, it is also possible to construct coherent explanations of income differences and long-run trends in economic growth.
    SSRN Electronic Journal 06/2005; DOI:10.1016/S1574-0684(05)01022-1
  • [Show abstract] [Hide abstract]
    ABSTRACT: We identified a family where five members had nonsyndromic ectrodactyly. There were three known instances of nonpenetrance. Although four individuals had unilateral cleft hand, one individual had more severe, bilateral and asymmetric absence of the digits. None had foot abnormalities. After exclusion of linkage of SHFM in this family to five known loci, a genome wide scan was performed with DNA from 5 affected and 15 unaffected members of this family. Suggestive evidence for linkage of ectrodactyly to 8q was obtained on the basis of a maximum LOD score of 2.54 at theta (max) = 0 with GAAT1A4. Critical recombinants place the ectrodactyly gene in this family in a 16 cM (21 Mb) interval between D8S1143 and D8S556. Mutational analysis of two candidate genes (FZD6, GDF6) did not identify any mutations in affected members of this family. Our data indicate further genetic heterogeneity for ectrodactyly and suggest the presence of an additional SHFM locus in chromosome region 8q21.11-q22.3.
    American Journal of Medical Genetics Part A 08/2006; 140(16):1744-8. DOI:10.1002/ajmg.a.31375 · 2.05 Impact Factor