42. A male mouse cell line has a large translocation from X chromosome into chromosome 1. When a GFP containing transgene is inserted in this chromosome 1 with translocation, it is often silenced. However when inserted in the other homologue of chromosome 1 that does not contain the translocation, it is almost always expressed. Which of the following phenomenon best describes this effect?
(1) Genome imprinting
(2) Gene balance
(3) Sex-specific expression
(4) Dosage compensation

The phenomenon best describing the silencing of a GFP transgene inserted in a chromosome containing a large X-to-chromosome 1 translocation, while being expressed in the other homolog without translocation, is dosage compensation. This mechanism equalizes gene expression between chromosomes, especially important for sex chromosome-linked genes, but can affect translocated segments to maintain balanced expression.

Explanation of Each Option

• Genome imprinting refers to parent-of-origin specific gene expression, where certain genes are epigenetically silenced based on whether they are inherited from the mother or father. It typically involves DNA methylation patterns regulating monoallelic expression but is unrelated to translocation-induced silencing in this context.

• Gene balance involves maintaining correct stoichiometry of gene products in the genome. Large chromosomal rearrangements can disrupt this balance. However, gene balance per se does not directly explain silencing of a transgene on the translocated chromosome.

• Sex-specific expression is gene expression differing between males and females. While the translocation involves the X chromosome (sex chromosome), the described silencing is more about chromosome structure and dosage effects than sex-specific regulatory differences.

• Dosage compensation is the process by which organisms equalize expression levels of genes on sex chromosomes (particularly X-linked genes) between sexes. In mammals, one X chromosome in females is inactivated to match gene dosage with males. A large translocation from the X chromosome to chromosome 1 can subject that region to silencing to equalize dosage effects, causing transgene silencing when inserted on the translocated chromosome but not on the non-translocated homologue.

Thus, dosage compensation best explains this phenomenon.

Introduction:
Chromosomal translocations involving the X chromosome can drastically affect gene expression patterns in mice. When a large segment of the X chromosome translocates to chromosome 1, the normal dosage compensation mechanisms may silence genes, including transgenes like GFP, inserted into the translocated region. However, the same transgene on the non-translocated homologue expresses normally. This article explains the underlying genetic phenomenon, comparing it with related concepts such as genomic imprinting, gene balance, and sex-specific expression to clarify why dosage compensation best describes this effect.

If you need detailed explanations for each of the four options:

• Genome imprinting involves parent-specific epigenetic silencing affecting gene expression, but it is unrelated to structural chromosome changes causing silencing.

• Gene balance maintains gene dosage equilibrium across chromosomes but does not explain preferential silencing on a translocated chromosome.

• Sex-specific expression accounts for differences in gene expression between males and females, generally without involving chromosomal rearrangements.

• Dosage compensation specifically regulates expression from sex chromosomes, often silencing one copy or regulating translocated segments to maintain balanced gene expression across chromosomes.

Therefore, the transgene silencing seen only on the chromosome with X-to-1 translocation is an example of dosage compensation in action, aimed at balancing gene expression in the presence of abnormal chromosomal arrangements.

This explanation is consistent with current genetic and epigenetic understanding of chromosomal translocations and their effects on gene regulation in mice.