The Drosophila sex-determination switch gene Sex-lethal (Sxl) and the X-chromosome signal element genes (XSEs) that induce the female-specific expression of Sxl are transcribed extremely early in development when most of the genome of this organism is still silent. The DNA sequence CAGGTAG had been implicated in this pre-cellular blastoderm activation of sex-determination genes. A genome-wide computational search, reported here, suggested that CAGGTAG is not specific to early sex-determination genes, since it is over-represented upstream of most genes that are transcribed pre-cellular blastoderm, not just those involved in sex determination. The same search identified similarly over-represented, one-base-pair degenerate sequences as possible functional synonyms of CAGGTAG. We call these heptamers collectively, the TAGteam. Relevance of the TAGteam sequences to pre-cellular blastoderm transcription was established through analysis of TAGteam changes in Sxl, scute (an XSE), and the 'ventral repression element' of the pattern-formation gene zerknüllt. Decreasing the number of TAGteam sites retarded the onset of pre-blastoderm transcription, whereas increasing their number correlated with an advanced onset. Titration of repressors was thought to be the rate-limiting step determining the onset of such early transcription, but this TAGteam dose effect shows that activators must also play an important role in the timing of pre-blastoderm gene expression.

The speed , accuracy , efficiency , and cost-effectiveness of DNA sequencing have been improving continuously since the initial derivation of the technique in the mid-1970s. With the advent of massively parallel sequencing technologies , DNA sequencing costs have been dramatically reduced. No longer is it unthinkable to sequence hundreds or even thousands of genes in a single individual with a suspected genetic disease or complex disease predisposition. Along with the benefits offered by these technologies come a number of challenges that must be addressed before wide-scale sequencing becomes accepted medical practice. Molecular diagnosticians will need to become comfortable with , and gain confidence in , these new platforms , which are based on radically different technologies compared to the standard DNA sequencers in routine use today. Experience will determine whether these instruments are best applied to sequencing versus resequencing. Perhaps most importantly , along with increasing read lengths inevitably comes increased ascertainment of novel sequence variants of uncertain clinical significance , the postanalytical aspects of which could bog down the entire field. But despite these obstacles , and as a direct result of the promises these sequencing advances present, it will likely not be long before next-generation sequencing begins to make an impact in molecular medicine. In this review , technical issues are discussed, in addition to the practical considerations that will need to be addressed as advances push toward personal genome sequencing. (J Mol

Because a significant proportion of critically ill neonates suffer the consequence of a genetic disorder, it is imperative that neonatologists be familiar with the phenotypes associated with the most common disorders and with the laboratory tests that help diagnose them. Currently available clinical tests detect a wide variety of genetic abnormalities ranging from defects in chromosome number to mutations as small as a single nucleotide. Recent advances also allow for comprehensive screening of candidate regions of the genome for pathogenic variants. However, when ordering any genetic laboratory test, the technical and analytical limitations of each assay need to be appreciated, as do other considerations, such as turnaround time and cost.

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