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Genetic diversity across the pseudoautosomal boundary varies across human populations

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Unlike the autosomes, recombination on the sex chromosomes is limited to the pseudoautosomal regions (PARs) at each end of the chromosome. PAR1 spans approximately 2.7 Mb from the tip of the proximal arm of each sex chromosome, and a pseudoautosomal

Unlike the autosomes, recombination on the sex chromosomes is limited to the pseudoautosomal regions (PARs) at each end of the chromosome. PAR1 spans approximately 2.7 Mb from the tip of the proximal arm of each sex chromosome, and a pseudoautosomal boundary between the PAR1 and non-PAR region is thought to have evolved from a Y-specific inversion that suppressed recombination across the boundary. In addition to the two PARs, there is also a human-specific X-transposed region (XTR) that was duplicated from the X to the Y chromosome. Genetic diversity is expected to be higher in recombining than nonrecombining regions, particularly because recombination reduces the effects of linked selection, allowing neutral variation to accumulate. We previously showed that diversity decreases linearly across the previously defined pseudoautosomal boundary (rather than drop suddenly at the boundary), suggesting that the pseudoautosomal boundary may not be as strict as previously thought. In this study, we analyzed data from 1271 genetic females to explore the extent to which the pseudoautosomal boundary varies among human populations (broadly, African, European, South Asian, East Asian, and the Americas). We found that, in all populations, genetic diversity was significantly higher in the PAR1 and XTR than in the non-PAR regions, and that diversity decreased linearly from the PAR1 to finally reach a non-PAR value well past the pseudoautosomal boundary in all populations. However, we also found that the location at which diversity changes from reflecting the higher PAR1 diversity to the lower nonPAR diversity varied by as much as 500 kb among populations. The lack of genetic evidence for a strict pseudoautosomal boundary and the variability in patterns of diversity across the pseudoautosomal boundary are consistent with two potential explanations: (1) the boundary itself may vary across populations, or (2) that population-specific demographic histories have shaped diversity across the pseudoautosomal boundary.

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2016-12

Characterizing Gene Expression in Human Tissues to Better Understand Sex Differences in Health and Disease

Description

The regulation of gene expression, timing, location, and amount of a given project, ultimately affects the cellular structure and function. More broadly, gene regulation is the basis for cellular differentiation and development. However, gene expression is not uniform among individuals

The regulation of gene expression, timing, location, and amount of a given project, ultimately affects the cellular structure and function. More broadly, gene regulation is the basis for cellular differentiation and development. However, gene expression is not uniform among individuals and varies greatly between genetic males and females. Males are hemizygous for the X chromosome, whereas females have two X chromosome copies. Contributing to the sex differences in gene expression between males and females are the sex chromosomes, X and Y. Gene expression differences on the autosomes and the X chromosome between males (46, XY) and females (46, XX) may help inform on the mechanisms of sex differences in human health and disease. For example, XX females are more likely to suffer from autoimmune diseases, and genetic XY males are more likely to develop cancer. Characterizing sex-specific gene expression among human tissues will help inform the molecular mechanisms driving sex differences in human health and disease. This dissertation covers a range of critical aspects in gene expression. In chapter 1, I will introduce a method to align RNA-Seq reads to a sex chromosome complement informed reference genome that considers the X and Y chromosomes' shared evolutionary history. Using this approach, I show that more genes are called as sex differentially expressed in several human adult tissues compared to a default reference alignment. In chapter 2, I characterize gene expression in an early formed tissue, the human placenta. The placenta is the DNA of the developing fetus and is typically XY male or XX female. There are well-documented sex differences in pregnancy complications, yet, surprisingly, there is no observable sex difference in expression of innate immune genes, suggesting expression of these genes is conserved. In chapter 3, I investigate gene expression in breast cancer cell lines. Cancer arises in part due to the disruption of gene expression. Here I show 19 tumor suppressor genes become upregulated in response to a synthetic protein treatment. In chapter 4, I discuss gene and allele-specific expression in Nasonia jewel wasp. Chapter 4 is a replication and extension study and discusses the importance of reproducibility.

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2021

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Comparative genomics and novel bioinformatics methodology applied to the green anole reveal unique sex chromosome evolution

Description

In species with highly heteromorphic sex chromosomes, the degradation of one of the sex chromosomes can result in unequal gene expression between the sexes (e.g., between XX females and XY males) and between the sex chromosomes and the autosomes. Dosage

In species with highly heteromorphic sex chromosomes, the degradation of one of the sex chromosomes can result in unequal gene expression between the sexes (e.g., between XX females and XY males) and between the sex chromosomes and the autosomes. Dosage compensation is a process whereby genes on the sex chromosomes achieve equal gene expression which prevents deleterious side effects from having too much or too little expression of genes on sex chromsomes. The green anole is part of a group of species that recently underwent an adaptive radiation. The green anole has XX/XY sex determination, but the content of the X chromosome and its evolution have not been described. Given its status as a model species, better understanding the green anole genome could reveal insights into other species. Genomic analyses are crucial for a comprehensive picture of sex chromosome differentiation and dosage compensation, in addition to understanding speciation.

In order to address this, multiple comparative genomics and bioinformatics analyses were conducted to elucidate patterns of evolution in the green anole and across multiple anole species. Comparative genomics analyses were used to infer additional X-linked loci in the green anole, RNAseq data from male and female samples were anayzed to quantify patterns of sex-biased gene expression across the genome, and the extent of dosage compensation on the anole X chromosome was characterized, providing evidence that the sex chromosomes in the green anole are dosage compensated.

In addition, X-linked genes have a lower ratio of nonsynonymous to synonymous substitution rates than the autosomes when compared to other Anolis species, and pairwise rates of evolution in genes across the anole genome were analyzed. To conduct this analysis a new pipeline was created for filtering alignments and performing batch calculations for whole genome coding sequences. This pipeline has been made publicly available.

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2016

Ericsson Method of Sperm Separation

Description

In 1973, Ronald Ericsson developed the Ericsson method, which is a technique used to separate human male sperm cells by their genetic material. Ericsson, a physician and reproduction researcher, developed the method while conducting research on sperm isolation in Berlin,

In 1973, Ronald Ericsson developed the Ericsson method, which is a technique used to separate human male sperm cells by their genetic material. Ericsson, a physician and reproduction researcher, developed the method while conducting research on sperm isolation in Berlin, Germany, in the early 1970s. He found that the sperm cells that carry male-producing Y chromosomes move through liquid faster than the cells that carry female-producing X chromosomes. As a result of his findings, Ericsson suggested suspending a semen sample in a viscous liquid made from albumin protein, and collecting only sperm that quickly pass through the liquid. Shortly after Ericsson described his method, researchers demonstrated that it was effective for sex selection. However, later studies contested those results. Despite that, the Ericsson method is still utilized by couples in 2018 as a means of sex selection and was the first sperm separation technique used in combination with artificial insemination to enable people to select the sex of their children.

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Date Created
2019-09-20

Curt Jacob Stern (1902-1981)

Description

Curt Jacob Stern studied radiation and chromosomes in humans and fruit flies in the United States during the twentieth century. He researched the mechanisms of inheritance and of mitosis, or the process in which the chromosomes in the nucleus of

Curt Jacob Stern studied radiation and chromosomes in humans and fruit flies in the United States during the twentieth century. He researched the mechanisms of inheritance and of mitosis, or the process in which the chromosomes in the nucleus of a single cell, called the parent cell, split into identical sets and yield two cells, called daughter cells. Stern worked on the Drosophila melanogaster fruit fly, and he provided early evidence that chromosomes exchange genetic material during cellular reproduction. During World War II, he provided evidence for the harmful effects of radiation on developing organisms. That research showed that mutations can cause problems in developing fetuses and can lead to cancer. He helped explain how genetic material transmits from parent to progeny, and how it functions in developing organisms.

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2017-06-23

Your Baby’s Sex: Now You Can Choose (1970), by David M. Rorvik and Landrum B. Shettles

Description

In the book Your Baby’s Sex: Now You Can Choose, David Michael Rorvik and Landrum Brewer Shettles describe methods that couples can use prior to and during conception that will increase the chances of producing a child of their desired

In the book Your Baby’s Sex: Now You Can Choose, David Michael Rorvik and Landrum Brewer Shettles describe methods that couples can use prior to and during conception that will increase the chances of producing a child of their desired sex. Rorvik, a science writer, and Shettles, an obstetrics and gynecology researcher and physician, co-wrote the book. Shettles developed the methods detailed in the book during the 1960s. Although the authors claim a high success rate, some researchers have contested the validity of the methods proposed in Your Baby’s Sex: Now You Can Choose. Despite contradicting evidence for the effectiveness of the methods, the book itself has remained popular throughout its forty consecutive years in print. Since its original publication, Your Baby’s Sex: Now You Can Choose has reached a large audience, with over 1.5 million copies of the book sold worldwide, while adding to the controversy about the ethics of sex selection research.

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2019-10-31

The Shettles Method of Sex Selection

Description

In the 1960s in the United States Landrum B. Shettles developed the Shettles method, which is a procedure for couples to use prior to and during an intercourse to increase their chances of conceiving a fetus of their desired sex.

In the 1960s in the United States Landrum B. Shettles developed the Shettles method, which is a procedure for couples to use prior to and during an intercourse to increase their chances of conceiving a fetus of their desired sex. Shettles, a physician, who specialized in obstetrics and gynecology, found a difference in the size and shape of male sperm cells that he correlated with the different sex chromosomes they carry. Based on that finding, Shettles developed procedures for couples to follow based on whether they desire a female or a male fetus and published them in the 1970 book, Your Baby’s Sex: Now You Can Choose. The Shettles method is based on the idea that male-producing sperm prefer alkaline conditions, whereas female-producing sperm prefer acidic conditions. The method provides couples with a procedure intended to enhance the favored environment for the sperm that will supposedly produce the desired sex, including female douches to be used before intercourse and how to time sexual intercourse within the female menstrual cycle. The book Your Baby’s Sex: Now You Can Choose, made the Shettles method a widely popular method of natural sex selection.

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Date Created
2019-04-03

"Male Development of Chromosomally Female Mice Transgenic for Sry gene" (1991), by Peter Koopman, et al.

Description

Early 1990s research conducted by Peter Koopman, John Gubbay, Nigel Vivian, Peter Goodfellow, and Robin Lovell-Badge, showed that chromosomally female (XX) mice embryos can develop as male with the addition of a genetic fragment from the Y

Early 1990s research conducted by Peter Koopman, John Gubbay, Nigel Vivian, Peter Goodfellow, and Robin Lovell-Badge, showed that chromosomally female (XX) mice embryos can develop as male with the addition of a genetic fragment from the Y chromosome of male mice. The genetic fragment contained a segment of the mouse Sry gene, which is analogous to the human SRY gene. The researchers sought to identify Sry gene as the gene that produced the testis determining factor protein (Tdf protein in mice or TDF protein in humans), which initiates the formation of testis. Koopman's team published their results in 1991 in Male Development of Chromosomally Female Mice Transgenic for Sry gene. Their results showed that Sry gene partly determines the sex of an embryo and is the only gene on the Y chromosome necessary for initiation of male development in mice.

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2014-01-28

Studies in Spermatogenesis (1905), by Nettie Maria Stevens

Description

Studies in Spermatogenesis is a two volume book written by Nettie Maria Stevens, and published by the Carnegie Institution of Washington in 1905 and 1906. In the books Stevens explains the research she conducted on chromosomal sex determination in the

Studies in Spermatogenesis is a two volume book written by Nettie Maria Stevens, and published by the Carnegie Institution of Washington in 1905 and 1906. In the books Stevens explains the research she conducted on chromosomal sex determination in the sperm and egg cells of insect species while at Bryn Mawr College, near Philadelphia, Pennsylvania. Studies in Spermatogenesis described early examples of chromosomal XY sex-determination.

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Date Created
2014-01-22

Theophilus Shickel Painter (1889-1969)

Description

Theophilus Shickel Painter studied the structure and
function of chromosomes in the US during in the early to mid-twentieth century. Painter worked at
the University of Texas at Austin in Austin, Texas. In the 1920s
and 1930s,

Theophilus Shickel Painter studied the structure and
function of chromosomes in the US during in the early to mid-twentieth century. Painter worked at
the University of Texas at Austin in Austin, Texas. In the 1920s
and 1930s, Painter studied the chromosomes of the salivary gland
giant chromosomes of the fruit fly (Drosophila
melanogaster), with Hermann J. Muller. Muller and Painter
studied the ability of X-rays to cause changes in the chromosomes
of fruit flies. Painter also studied chromosomes in mammals.
He investigated the development of the male gamete, a process
called spermatogenesis, in several invertebrates and vertebrates,
including mammals. In addition, Painter studied the role the
Y-chromosome plays in the determination and development of the male
embryo. Painter's research concluded that egg cells fertilized by
sperm cell bearing an X-chromosome resulted in a female embryo,
whereas egg cells fertilized by a sperm cell carrying a
Y-chromosome resulted in a male embryo. Painter's work with
chromosomes helped other researchers determine that X- and
Y-chromosomes are responsible for sex determination.

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Date Created
2014-11-22