Mapping of prolactin and tumor necrosis factor-beta genes on human chromosome 6p using lymphoblastoid cell deletion mutants

Abstract

A collection of human B lymphoblastoid cell lines (LCLs) was used to map two genetic sequences for which polymorphism had not been identified: human prolactin (PRL) and tumor necrosis factor-beta (TNFB). The LCLs have overlapping deletions on chromosome 6p produced by gamma-irradiation of LCL 721. After using two chromosome 6p sequences for which LCL 721 is heterozygous to validate our scanning densitometry (SD) method for inferring gene copy number, SD was used to map TNFB and PRL. TNFB maps to the interval between the C4 complement and HLA-B loci within the MHC on chromosome 6p. PRL lies within the 6p21.3-6p22.2 interval distal to HLA-C. We found that LCL 721 is heterozygous for PRL DNA fragment lengths generated by HpaII but not MspI digestion, indicating that the two copies of PRL in LCL 721 are differentially methylated. This novel methylation RFLP was used to corroborate the region PRL assignment.

Big Prolactin 60 kDa is Overexpressed in Salivary Glandular Epithelial Cells from Patients with Sjögren's Syndrome

“…More interesting is the close genomic linkage between HLA alleles and the prolactin gene. Indeed, human prolactin gene is located on chromosome 6 (Owerbach et al, 1981), more particularly in the interval 6p22.2 to p21.3 (Evans et al, 1989) close to specific HLA alleles. This regional assignment is of interest because a recent study (Brennan et al, 1997) presented data that there may be linkage disequilibrium between HLA-DRB1 alleles and microsatellite marker close to the prolactin gene among women with rheumatoid arthritis and systemic lupus erythematosus.…”

Macroprolactin: searching for a needle in a haystack?

“…The human prolactin gene (PRL) gene, located on chromosome 6p22.3 [2], encodes for a 220 aminoacids, 23 kDa monomeric protein originating from cleavage of the 26 kDa preprolactin molecule, which is mainly produced by the cells of the anterior pituitary and placenta, precisely by those of the decidualized endometrium [3]. The hormone has essential functions in regulating breast development and milk production in women, but also plays pleiotropic functions as osmoregulation, angiogenesis and immunoregulation [4].…”

Characterization of a prolactin gene polymorphism and its associations with systemic lupus erythematosus

“…The human prolactin gene is situated on the short arm of chromosome 6, close to the major histocompatibility complex (MHC) (33). Previous studies have found linkage disequilibrium between MHC genes known to be associated with rheumatoid arthritis and SLE (34), raising the possibility that polymorphisms in the upstream regulatory regions of the human prolactin gene, which perhaps determine levels of lymphocyte-specific transcription, might be associated with disease.…”