Imbalance in Gene Expression

Figure 3-11 Allelic expression patterns for a gene sequence with a transcribed DNA variant (here, a C or a T) to distinguish the alleles. As described in the text, the relative abundance of RNA transcripts from the two alleles (here, carrying a G or an A) demonstrates whether the gene shows balanced expression (top), allelic imbalance (center), or exclusively monoallelic expression (bottom). Different underlying mechanisms for allelic imbalance are compared in Table 3-2. SNP, Single nucleotide polymorphism.


Allelic Imbalance in Gene Expression


Monoallelic Gene Expression

Somatic Rearrangement

This mechanism of somatic rearrangement and random monoallelic gene expression is also observed at the T-cell receptor genes in the T-cell lineage. However, such behavior is unique to these gene families and cell lineages; the rest of the genome remains highly stable throughout development and differentiation.

Random Monoallelic Expression

Parent-of-Origin Imprinting

Imprinting takes place during gametogenesis, before fertilization, and marks certain genes as having come from the mother or father (Fig. 3-12). After conception, the parent-of-origin imprint is maintained in some or all of the somatic tissues of the embryo and silences gene expression on allele(s) within the imprinted region; whereas some imprinted genes show monoallelic expression throughout the embryo, others show tissue-specific imprinting, especially in the placenta, with biallelic expression in other tissues. The imprinted state persists postnatally into adulthood through hundreds of cell divisions so that only the maternal or paternal copy of the gene is expressed. Yet, imprinting must be reversible: a paternally derived allele, when it is inherited by a female, must be converted in her germline so that she can then pass it on with a maternal imprint to her offspring. Likewise, an imprinted maternally derived allele, when it is inherited by a male, must be converted in his germline so that he can pass it on as a paternally imprinted allele to his offspring (see Fig. 3-12). Control over this conversion process appears to be governed by specific DNA elements called imprinting control regions or imprinting centers that are located within imprinted regions throughout the genome; although their precise mechanism of action is not known, many appear to involve ncRNAs that initiate the epigenetic change in chromatin, which then spreads outward along the chromosome over the imprinted region. Notably, although the imprinted region can encompass more than a single gene, this form of monoallelic expression is confined to a delimited genomic segment, typically a few hundred kilobase pairs to a few megabases in overall size; this distinguishes genomic imprinting both from the more general form of random monoallelic expression described earlier (which appears to involve individual genes under locus-specific control) and from X chromosome inactivation, described in the next section (which involves genes along the entire chromosome).


Figure 3-12 Genomic imprinting and conversion of maternal and paternal imprints during passage through male or female gametogenesis. Within a hypothetical imprinted region on an pair of homologous autosomes, paternally imprinted genes are indicated in blue, whereas a maternally imprinted gene is indicated in red. After fertilization, both male and female embryos have one copy of the chromosome carrying a paternal imprint and one copy carrying a maternal imprint. During oogenesis (top) and spermatogenesis (bottom), the imprints are erased by removal of epigenetic marks, and new imprints determined by the sex of the parent are established within the imprinted region. Gametes thus carry a monoallelic imprint appropriate to the parent of origin, whereas somatic cells in both sexes carry one chromosome of each imprinted type.

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Nov 27, 2016 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Imbalance in Gene Expression

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