The gene spans 36 kb on the short arm of chromosome 20. It contains 26 exons (size from 28 bp to 2 kb) and 25 introns (size from 89 bp to nearly 9 kb) : table 1. Intron 19 contains a CA dinucleotide repeat which is a highly polymorphic marker : D20S1154 (12 alleles with heterozygosity of 85.8% and PIC of 0.844).

Size of exons and introns of the human JAG1 gene
exon 1 : 494; intron 1 : 443; exon 2 : 306; intron 2 : 8686; exon 3 : 52; intron 3 : 5240; exon 4 : 255; intron 4 : 2009; exon 5 : 61; intron 5 : 3799; exon 6 : 131; intron 6 : 217; exon 7 : 120; intron 7 : 436; exon 8 : 114; intron 8 : 1220; exon 9 : 114; intron 9 : 611; exon 10 : 114; intron 10: 414; exon 11 : 47; intron 11 : 338; exon 12 : 174; intron 12 : 438; exon 13 : 151; intron 13 : 856; exon 14 : 165; intron 14 : 854; exon 15 : 114; intron 15 : 501; exon 16 : 114; intron 16 99; exon 17 : 114; intron 17 : 163; exon 18 : 117; intron 18 : 478; exon 19 : 28; intron 19 : 493; exon 20 : 86; intron 20 : 1176; exon 21 : 114; intron 21 : 595; exon 22 : 110; intron 22 : 89; exon 23 : 234; intron 23 : 215; exon 24 : 132; intron 24 : 179; exon 25 : 151; intron 25 : 827; exon 26 : 1979

Polymorphisms were described in the cDNA sequence (table 1).

JAG1 is transcribed from centromere to telomere. The 26 exons are coding ; exon 1 is coding on the last 81 bases, and exon 26 on the first 455 bases. The transcript size is 5.5 kb.

glycosylated transmembrane protein ; 1218 amino acids,
predicted glycosylation sites : 960; 991; 1045; 1064.
Apparent size on Western blot : about 180 kDa.

very wide; in heart, arteries, kidney, lung, pancreas, skeletal muscle, central nervous system, limb bud, etc. during embryonic and fetal development ; in adult tissues ; in tumors.

transmembrane plasma protein

ligand of the NOTCH family of receptors. The Notch signaling pathway plays a crucial role during embryonic pattern formation, controls many conserved cell determination events and defines a fundamental mechanism controlling cell fate. It is involved in lineage cell decisions in a variety of tissues. It plays a role in hematopoiesis, vascular development and angiogenesis, myogenesis, neurogenesis, somitogenesis ; kidney, eye, ear, and tooth development etc.

Heterozygous mutations in JAG1 gene cause Alagille syndrome.
Five per cent are deletions on the short arm of chromosome 20 that could be visible in cytogenetics : the whole gene or part of the gene, or a region larger than the gene can be deleted. : del(20p), del(20)(p11.2), del(20)(p12.3-p11.23), del(20)(p13-p12.2), ins(7;20), t(2;20).
Ninety five per cent are point intragenic mutations that are spread over the entire gene, with the exception of the part of the gene encoding the intracellular part of the protein (see the structure of the protein in Figure 2). Seventy per cent of mutations are nonsense or frameshift mutations leading to premature stop codons ; 15% are missense mutations and 14% are splice site mutations (Figure 3). The most frequent mutation ( "delCAGT" in exon 17) accounts for 5% of all mutations.
Some AGS probands present with no mutation in the DNA of the 26 exons and exon boundaries of JAG1. In those instances, no prenatal diagnosis can be performed.

Most mutations (70%) are de novo

Cases of mosaicisms are described