Exploring the Biological Contributions to Human Health Does Sex Matter? (2001) / Chapter Skim
Currently Skimming:
2 Every Cell Has a Sex
2 Every Cell Has a Sex
Pages 28-44
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 28... ...
Genes on the sex chromosomes can be expressed differently between males and females because of the presence of either single or double copies of the gene and because of the phenomena of different meiotic effects, X inactivation, and genetic imprinting. The inheritance of either a male or a female genotype is further influenced by the source (maternal or paternal)
|
From page 29... ...
In the second model (which is not necessarily exclusive of the first one) , one or more genes, located on the sex chromosomes and thus expressed differently in the two sexes, encode proteins involved in ratelimiting or rate-influencing steps in biochemical or physiological pathways that are critical to establishing differences between the sexes.
|
From page 30... ...
30 EXPLORING THE BIOLOGICAL CONTRIBUTIONS TO HUMAN HEALTH Model I Hormones Model Ha Model rib Gene Expression in: Male Female Gene 1 Gene 2 Gene 3 Gene 'N' Male A ~ B Female A ~ B Male A Female A tt t | X-linked gene product | C ~ D C ~ D I Y-linked gene product B B C ~ D C ~ D FIGURE 2-1 Schematic representation of two general models used to explain sex differences in gene expression. In Model I, hormones in males and females differentially influence the level of expression of different genes (Gene 1 to Gene N)
|
From page 31... ...
Although the process of X-chromosome inactivation equalizes the effective dosage of most X-chromosome genes between male and female cells by inactivating one of the two X chromosomes in female cells, not all genes on the inactivated X chromosome
|
From page 32... ...
More difficult will be determination of the relative effects of differences in gene expression on the characteristic phenotypic differences seen between males and females. Nonetheless, this new technology with DNA arrays promises to provide a comprehensive functional view of the genome in different cellular states, and studies that address differences in expression throughout the male and female genomes should reap a rich harvest.
|
From page 33... ...
Because the sex chromosomes comprise approximately 5 percent of the total human genome (Figure 2-2) , there is the potential for 1 in 20 biochemical reactions to be differentially affected in male versus female cells.
|
From page 34... ...
The remainder of the Y chromosome (the Y-chromosome-specific portion) does not recombine with the X chromosome and strictly comprises "Y-chromosome-linked DNA" (although some of the nonrecombining part of the Y chromosome retains residual homology to X-chromosome-linked genes, reflecting the shared evolutionary history of the two sex chromosomes [see billowy.
|
From page 35... ...
Deletion or mutation of some of these genes has been implicated in cases of male infertility, but otherwise, these genes have no obvious phenotypic effects (Kent-First et al., 1999; McDonough, 1998~. Females Have Two X Chromosomes, Males Have One Male and female genomes also differ in the other sex chromosome, the X chromosome, in that females have twice the dose of X-chromosomelinked genes that males have.
|
From page 36... ...
or stochastic variation in the proliferation of cells, in which one or the other X chromosome has been inactivated. The phenotype observed in females heterozygous for X-chromosome-linked traits can also vary widely, with an increasing level of clinical expression or increasing severity correlating with the proportion of cells expressing a mutant allele from the active X chromosome.
|
From page 37... ...
X-chromosome inactivation is associated with extensive silencing of genes on the affected X chromosome and occurs in almost every cell of XX females but does not occur in XY males. The one documented exception to this rule occurs, reciprocally, in reproductive cells; the single X chromosome of males becomes heterochromatic in spermatocytes, whereas both X chromosomes are thought to be active in primary oocytes.
|
From page 38... ...
, individual females have two epigenetically distinct populations of cells: those in which the maternally derived X chromosome remains active and those in which the paternally derived X chromosome remains active (Figure 2-3~. By contrast, males have only an active maternally derived X chromosome in all of their cells.
|
From page 39... ...
It has been suggested that some of these differences may lead to sex-specific levels of risk for certain diseases, such as the suspected relationship between gastrin-releasing peptide receptor and smoking-related lung cancer (Shriver et al., 2000~. Gastrin-releasing peptide is expressed by both the active and the inactive X chromosomes, and elevated levels of gastrin-releasing peptide are hypothesized to be associated with an elevated risk of lung cancer in women who smoke.
|
From page 40... ...
Because autosomes are transmitted equally to both sexes, it is not predicted that inheritance of imprinted genetic information on the autosomes should have a differential effect on male versus female offspring. The situation is different for sex chromosomes.
|
From page 41... ...
This simple numerical difference in the number of stem cell divisions between the two sexes dictates that most mutations resulting from errors in DNA replication take place in the male germ line (Haldane, 1935) , although the magnitude of this difference and whether additional factors may contribute are subjects of debate (Hurst and Ellegren, 1998~.
|
From page 42... ...
but may be due to a number of causes, including meiotic drive, preferential cosegregation of sex chromosomes with one of a pair of homologous chromosomes, preferential fertilization, and preferential death of the embryo of one sex. These biases that are specific to the sex of the offspring have been observed as a result of transmission through both male and female parents (reviewed by Sapienza [1994~.
|
From page 43... ...
For example, the manipulations involved with introducing the new DNA sequence can sometimes introduce unexpected genetic changes, either at the locus under study or at unrelated loci. In addition, identical transgene or knockout models may have variable phenotypes, depending on the strain's background (just as for "normal" mutant alleles)
|
From page 44... ...
· Male and female germ cells differentially imprint the genetic information to be transmitted to their progeny. These findings argue that there are multiple, ubiquitous differences in the basic cellular biochemistry of males and females that can affect an individual's health.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.