Ch 7: Non-Mendelian Inheritance

Maternal Effect Genes

Maternal effect refers to an inheritance pattern for certain nuclear genes in which the genotyoe of the mother directly determines the phenotype of the offspring (161) Genotypes of father and offspring don't matter at all. Female gametes and gene products from mother Non-Mendelian pattern of inheritance can be explained by ooogenesis in female animals (162). As an oocyte matures, nurse cells surround and provide the egg w/nutrients and other materials. The gene products of the nursre cells, which reflect mother's genotype, influence early develpmental stages of embryo, The sperm's genotype is irrelevant because the sperm's gene comes in too late (163). Maternal effect genes code for proteins that are important in early steps of embryogenesis (163-164) Accumulation of genes in the egg allows embryogenesis to proceed quickly after fertilization (164).  Maternal effect genes often play a role in cell division, cleavage patterns, and body axis orientation, so defective alleles in these genes tend to have a deamatic effect on phenotype (164).

Epigenetic Inheritance

Epigenetic inheritance is a patten in which a modificatio occurs to a nuclear gene or chromosome that alters gene expression, but is not perminant oer the vourse of many generations (164), Dosage compensation Dosage compensation refers to the phenomenon that the level of expression of many genes on the sex chromosomes is similar in both sexes even though males and females have a different complement of SEX CHROMOSOMES (164)   One copy in the female is not equivalent to 1 copy in the male. Difference in gene dosage is being compensated at level of gene expression. females equalize the expression X-llinked genes by turning of one of X chromosomes, called X inactivation (164) Dosage compensation and X-inactivation Barr bodies are highly condensed structures in the interphase of somatic cells. Barr bodies are highly condensed X chromosomes (165). One of 2 of those are activated early in embryonic development, which contributes to the calico cat color.  During inactivation, the chromosomal DNA becomes highly compacted, so most of the genes cannot be expressed (166). When cell divisiob occurs and inactivated X is replicatied, X inactivation is passed along to future somatic cells. 

X Inactivation

X-inactivation center and Xist gene   A short region on the X chromosome called the X-inactivation center (Xic) s known to play a critical role in inactivation, (169). Counting of human X chromsomes is accomplished by counting the number of Xics (169) An Xic must be found for inactivation to occur (169), The gene within Xic that contols x-INACTIVATION is called the Xist gene.  (169) This is active on the inactivated X chromosome. Produces a molecule that coats the X chromosome and inactivates it.  After coating, other proteins assicuate with the Xist RNA and promote chromosomal compaction into a Barr body.  Another gene found within Xic is Tsix. This also plays a role in X inactivation (169) Overlaps with Xist and is transcribed in an opposite direction.  Role not completely understood, but it appears to decrease expression of Xist. On inactive X it is not expressed.  X chromosomes carrying a mutated form of tgis are preferentially inactivated. The X chromosomal controlling element (Xce) also affects the choice of X chromosome to be inactivated (169) Genetic variation in this gene- X chromosome carrying stronlg Xce is more likely to remain acive, thereby leading to skewed X inactivation.  Very close to end of Xic Mechanism is not well understood, but it might serve as abinding site proteins that regulate expression of genes in Xic. Genetic variation in Xce that enhances Xist expression would promote Barr body formation, whereas Xce variation that enhances Tsix expression preevents X inactivation.  3 phases of X inactivation (169): Initiation: One of the X chromosomes is targeted to remain active. Occurs during embryonic development. Spreading: Chosen X chromosome is inacivated, which requires expression of Xist gene. Xist RNA coats inactivated X and recruits proteins that promote compaction. Compaciton occurs via modification of histone proteins.\ Also occurs during embryonic development. Maintenance: Inactivated X chromosome is maintained during future cell divisions Some genes on inactivated X are expressed in somatic cells of adult female mammals (169), 

Genomic Imprinting

Expression depends on sex of parent Genomic imprinting refers to an analogous situation in which a segment of DNA is marked, and that mark isr etained and recognized throughout the life of the organism inheriting the marked DNA (170). Phenotypes follow non-Mendelian pattern of inheritance because the marking process causes offspring to distinguish between maternally and paternally inherited allels,. Depending on how genes are marked, offspring may only express 1 of 2 alleles (monoalleleic expression) (170). At the cellular level, this is how imprinting occurs: Establishment of imprint during gametogenesis Maintenance of imprint during embryogenesis and in adult somatic cells Erasure and reestablishment of the imprint in germ cells. Genomic imprinting is perminent in somatic cells, but the marking of alleles can be altered from generation to generation (171) In certain species, imprinting plays a role in the choice of which X chromosome is inactivated (172). Marking process involves DNA methylation Genomic imprinting involves a differentially methylated region (DMR) that is located near the imprinted gene (172). Methylated in sperm or egg, but not both. For most (but not all) genes, methylation at a DMR results in inhibition of geneexpression (172)