Structure of the human Na+/glucose cotransporter gene SGLT1.

Intestinal uptake of dietary glucose and galactose is mediated by the SGLT1 Na +/glucose cotransporter of the brush border.
An SGLT1 missense mutation underlies hereditary glucose/galactose malabsorption, characterized by potentially fatal diarrhea; conversely, oral rehydration therapy exploits normal transport to alleviate life-threatening diarrhea of infectious origin.
We have mapped the entire human SGLT1 Na +/glucose cotransporter gene from cosmid and lambda phage clones representing a genomic region of 112 kilobases.
Transcription initiation occurred from a site 27 base pairs 3 of a TATAA sequence.
All exon-flanking regions were sequenced, and the entire 112-kilobase region mapped with four restriction enzymes.
SGLT1 is comprised of 15 exons (spanning 72 kilobases); a possible evolutionary origin from a six-membrane-span ancestral precursor via a gene duplication event is suggested from comparison of exons against protein secondary structure and from sequence considerations.
A new missense mutation in exon 1 causing glucose/galactose malabsorption is also described.
This is the first Na (+) -dependent cotransporter gene structure reported.
These data facilitate the search for new glucose/galactose malabsorption-related mutations in this important gene and provide a basis for future evolutionary comparisons with other Na (+) -dependent cotransporters.. 
