Trends in Genetics
Volume 29, Issue 10, October 2013, Pages 569-574
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Opinion
Human housekeeping genes, revisited

https://doi.org/10.1016/j.tig.2013.05.010Get rights and content

Highlights

  • Most human genes are expressed in all tissues to some extent

  • Housekeeping genes may be defined by constant level of expression across tissues

  • We use RNA-seq data to provide a list of 3804 human housekeeping genes

  • Several exceptionally uniform genes are suggested as control genes for RT-PCR.

Housekeeping genes are involved in basic cell maintenance and, therefore, are expected to maintain constant expression levels in all cells and conditions. Identification of these genes facilitates exposure of the underlying cellular infrastructure and increases understanding of various structural genomic features. In addition, housekeeping genes are instrumental for calibration in many biotechnological applications and genomic studies. Advances in our ability to measure RNA expression have resulted in a gradual increase in the number of identified housekeeping genes. Here, we describe housekeeping gene detection in the era of massive parallel sequencing and RNA-seq. We emphasize the importance of expression at a constant level and provide a list of 3804 human genes that are expressed uniformly across a panel of tissues. Several exceptionally uniform genes are singled out for future experimental use, such as RT-PCR control genes. Finally, we discuss both ways in which current technology can meet some of past obstacles encountered, and several as yet unmet challenges.

Section snippets

The concept of housekeeping genes

Housekeeping genes are genes that are required for the maintenance of basal cellular functions that are essential for the existence of a cell, regardless of its specific role in the tissue or organism. Thus, they are expected to be expressed in all cells of an organism under normal conditions, irrespective of tissue type, developmental stage, cell cycle state, or external signal. From a fundamental point of view, full characterization of the minimal set of genes required to sustain life is of

Early detection schemes for housekeeping genes

The notion of housekeeping genes has been in use in the literature for nearly 40 years. In particular, several mammalian genes have been used widely as internal controls in experimental expression studies, such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), tubulins, cyclophilin, albumin, actins, 18S rRNA or 28S rRNA. Yet, only at the turn of the 21st century, with the advancement of transcriptome profiling technology, did it become possible to identify, systematically, a set of

Housekeeping genes in the deep-sequencing era

New horizons are opening as deep-sequencing technology takes over microarrays as the method of choice for transcriptome profiling [36]. RNA-seq was found to be preferable to microarrays as a tool for expression measurement. Unlike microarrays, RNA-seq does not require pre-knowledge of the genomic sequence (although it is helpful for analysis), and requires smaller amounts of RNA. It provides information at the single-base level, enabling better assessment of alternative splicing and even

Extracting a set of housekeeping genes from Human BodyMap data

Here, we demonstrate the power of the new technology for identifying housekeeping genes by analyzing expression data from the Human BodyMap (HBM) 2.0 Project. This includes publicly available RNA-Seq data (GEO accession number GSE30611, HBM), generated on HiSeq 2000 instruments, providing expression profiling in 16 normal human tissue types: adrenal, adipose, brain, breast, colon, heart, kidney, liver, lung, lymph, ovary, prostate, skeletal muscle, testes, thyroid, and white blood cells. Two

Concluding remarks

Current technology enables global measurement of expression levels with unprecedented accuracy. This advancement has revealed that large parts of the genome are normally expressed at a low level. Accordingly, we found that most human exons are expressed at some level in all the human tissues studied. This new technological era calls the community to reevaluate the concept of a housekeeping gene. Here, we have presented our own perspective, suggesting the use of low expression variation as the

Acknowledgments

We thank Ami Haviv and Gilad Finkelstein for help with reads’ alignments, and Lily Bazak for help in gene lengths’ analysis. This work was supported by Israel Science Foundation 379/12 (EE), by the I-CORE Program of the Planning and Budgeting Committee and the Israel Science Foundation (grant No 41/11) and by the Marie Curie Integration Grant 256593(EYL).

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