The lactase persistence/non-persistence polymorphism is controlled by a cis-acting element.
The lactase persistence/non-persistence polymorphism is controlled by a cis-acting element.
复制标题
乳糖酶持久性/非持久性多态性由顺式作用元件控制。
DOI：
10.1093/hmg/4.4.657
复制
发表时间：
1995
影响因子：
3.5
通讯作者：
D. Swallow
中科院分区：
文献类型：
--
作者：
Y. Wang;C. Harvey;W. S. Pratt;V. Sams;M. Sarner;M. Rossi;S. Auricchio;D. Swallow
乳糖酶活性在一些成年人的小肠中以高水平存在，而其他人则没有。这是由于遗传决定的多态性影响乳糖酶基因表达的发育调节。这种多态性与营养方面的文化差异有关，但尽管进行了详尽的研究，其分子基础仍未被发现，甚至还没有表明这种序列差异是存在于乳糖酶基因本身内部或附近，还是存在于反式作用因子中。因此，我们利用乳糖酶基因外显子内已知的DNA“标记”多态性来检查来自持续性和非持续性的人的单个乳糖酶mRNA转录本的表达。我们的研究结果表明，在某些乳糖酶持续性个体中，乳糖酶基因的一个等位基因的表达水平比另一个低得多，这些个体倾向于具有中等乳糖酶活性。有人提出，这些人是乳糖酶持久性和非持久性等位基因的杂合子，这意味着负责乳糖酶持久性/非持久性多态性的核苷酸取代是顺式作用的。这大大缩小了需要搜索相关序列差异的基因组区域。
Lactase activity is present at high levels in the small intestine of some human adults and not others. This is due to a genetically determined polymorphism which affects the developmental regulation of the expression of the lactase gene. This polymorphism is of considerable interest in relation to cultural differences in nutrition but despite exhaustive studies, the molecular basis has not yet been found. It has not even been shown whether the sequence differences reside within or adjacent to the lactase gene itself or in a trans-acting factor. We have therefore exploited known DNA 'marker' polymorphisms within the exons of the lactase gene to examine the expression of the individual lactase mRNA transcripts from persistent and non-persistent individuals in order to determine whether the regulation is in cis or trans. Our results show that in certain lactase persistent individuals one allele of the lactase gene is expressed at much lower levels than the other and these individuals tend to have intermediate lactase activities. It is proposed that these people are heterozygous for the lactase persistence and non-persistence alleles and that this means that the nucleotide substitutions responsible for the lactase persistence/non-persistence polymorphism are cis-acting. This narrows down considerably the area of the genome that needs to be searched for the relevant sequence differences.