Sex chromatin bodies Barr body Organism n n

Sex chromatin bodies Barr body

Organism n n n Human Chimpanzee Dog Horse Chicken Goldfish Fruit fly Mosquito Nematode Horsetail Sequoia Round worm No. chromosomes 46 48 78 64 78 94 8 6 11(m), 12(f) 216 22 2

What Exactly is a chromosome? Chromosomes are bodies present in visible during cell the rod-shaped, filamentous the nucleus, which become division. They are the carriers of the gene or unit of heredity. Chromosome are not visible in active nucleus due to their high water content, but are clearly seen during cell division.

n n Chromosomes were first described by Strausberger in 1875. The term “Chromosome”, however was first used by Waldeyer in 1888. They were given the name chromosome (Chromo = colour; Soma = body) due to their marked affinity for basic dyes. Their number can be counted easily only during mitotic metaphase.

This X-Y system of mammals is not the only chromosomal mechanism of determining sex. n Other options include the X-0 system, the Z-W system, and the haplodiploid system. n

Barr Bodies 1940’s two Canadian scientists noticed a dark staining mass in the nuclei of cat brain cells n Found these dark staining spots in female but not males n This held for cats and humans n They thought the spot was a tightly condensed X chromosome n

Barr Bodies Barr bodies represent the inactive X chromosome and are normally found only in female somatic cells.

X Inactivation of Females n During embryonic development one X chromosome becomes inactive (Barr Body). n All mitotic divisions create cells with the same inactive X. n Males and females have equal dose of gene representation

Dosage Compensation Sex Chromosomes: females XX, males XY n Females have two copies of every X-linked gene; males have only one. n How is this difference in gene dosage compensated for? OR n How to create equal amount of X chromosome gene products in males and females? n

Dosage Compensation To compensate for females having 2 X chromosomes vs. males having only 1 X chromosome could do one of two things : • Double the amount of transcription of X-chromosome genes in males. OR • Inactivate one of the X-chromosomes in females.

n Levels of enzymes or proteins encoded by genes on the X chromosome are the same in both males and females n Even though males have 1 X chromosome and females have 2.

n. A woman with the chromosome constitution 47, XXX should have 2 Barr bodies in each cell. n. XXY individuals are male, but have a Barr body. XO individuals are female but have no Barr bodies. n

46, XX 45, X 47, XXY 47, XXX 48, XXXX 1 Barr body 0 Barr body 1 Barr body 2 Barr bodies 3 Barr bodies # Barr bodies = N-1 (N = # X cs. present)

n G 6 PD, glucose 6 phosphate dehydrogenase, gene is carried on the X chromosome n This gene codes for an enzyme that breaks down sugar which helps red blood cells work properly. n Females produce the same amount of G 6 PD enzyme as males n XXY and XXX individuals produce the same about of G 6 PD as anyone else

Dosage compensation

n In cells with more than two X chromosomes, only one X remains genetically active and all the others become inactivated. n In some cells the paternal allele is expressed n In other cells the maternal allele is expressed n In XXX and XXXX females and XXY males only 1 X is activated in any given cell the rest are inactivated

X-inactivation

n Which chromosome is inactive is a matter of chance, but once an X has become inactivated , all cells arising from that cell will keep the same inactive X chromosome. n In human embryos, sex chromatin bodies have been observed by the 16 th day of gestation.

Mechanism of X-chromosome Inactivation n A region of X chromosome near the centromere called the X-inactivation center (XIC) is the control unit. This region contains the gene for X-inactive specific transcript (XIST RNA). The Xist gene is the only gene which is expressed from the Xi but not from the Xa. The silencing of genes along the Xi occurs soon after coating by Xist RNA. (repressive ) n n The Xi has high levels DNA methylation locks the chromosome in the inactive state. (associated with gene silencing )

n This occurs about 16 days after fertilization in a female embryo. n The process is independent from cell to cell. n A maternal or paternal X is randomly chosen to be inactivated.

Rollin Hotchkiss first discovered methylated DNA in 1948. n He found that DNA from certain sources contained, in addition to the standard four bases, a fifth: 5 -methyl cytosine. n It took almost three decades to find a role for it. n In the mid-1970 s, Harold Weintraub and his colleagues noticed that active genes are low in methyl groups or under methylated. n Therefore, a relationship between under methylation and gene activity seemed likely, as if methylation helped repress genes. n

This would be a valuable means of keeping genes inactive if methylation passed on from parent to daughter cells during cell division. n Each parental strand retains its methyl groups, which serve as signals to the methylating apparatus to place methyl groups on the newly made progeny strand. n Thus methylation has two of the requirements for mechanism of determination: n 1. It represses gene activity n 2. It is permanent. n

n To check this hypothesis Peter Jones and Lawrence Shapiro grew cells in the presence of drug 5 azacytosine, which prevents DNA methylation. This reactivated the lyonized (Mary lyon) the X chromosome. n Furthermore, Shapiro showed these reactivated chromosomes could be transferred to other cells and still remain active. n

X-inactivation facts about calico cats

What determines maleness and femaleness in humans? 2 possibilities: 1. Two X chromosomes are needed to make a female. If you have one X chromosome then you default to male. No, not the mechanism. 2. The Y chromosome is needed to make a male. Lack of the Y chromosome and you default to female. Yes, this is the mechanism.

X-chromosome 22. 3 22. 2 22. 1 p 21. 3 21. 2 21. 1 11. 4 11. 3 11. 22 11. 21 11. 2 12 13 pseudoautosomal region that escapes Xinactivation Duchenne Muscular Dystrophy locus X-inactivation center, XIST 21. 3 q critical region for ovarian development 24 25 26 27 28 p q 11. 3 11. 2 11. 1 11. 221 11. 222 11. 223 11. 23 12 21. 1 21. 2 22. 1 22. 2 22. 3 23 Y-chromosome Fragile X (FMR-1) locus pseudoautosomal region SRY (testes determining factor) AZF (azoospermia factor) (sperm development) heterochromatin

Presence of Barr bodies in a buccal smear was introduced by the International Olympic Committee Medical Commission as a sex determination (gender verification) test in 1968. This test, known as the Barr test or buccal smear sex test, was responsible for excluding about one female competitor in 400 from international competition. Six female competitors failed the test in the 1984 Los Angeles Olympic games. At the 1992 Barcelona Olympics, the Barr test was replaced by the polymerase chain reaction test.

Someone with a mutation in the SRY gene can develop into a female even though there are SRY and the Y chromosome are present. In rare cases, the SRY gene can be transferred to the X chromosome by chromosomal crossover during the production of sperm, and the resulting XX individual would be phenotypically male.

During the 1992 Olympics five women failed the PCR test; in 1996, eight. Testicular feminization syndrome (TFS), a genetic condition in which an XY (male) zygote develops as a phenotypically female adult, due to failure of androgen receptors (Androgen insensitivity syndrome AIS).

Dora Ratjen , November 20, 1918 Bremen , Germany - April 22, 2008) was a German athlete who competed for Germany in the Women's High Jump at the 1936 Summer Olympics at Berlin , finishing fourth, but was later discovered to be male.

Stella Walsh won a silver medal at the 1936 Olympics - but was later found to be a man Stella Walsh was killed in a random act of violence in 1968. 9 As part of a routine autopsy, coroners discovered that Stella was a masculine pseudohermaphrodite (mosaicism)

800 m gold medal in Berli 2009 Semenya ( south Africa) told to take gender test Reports in two newspapers in September said the results of the tests showed Semenya has both male and female characteristics. The IAAF has declined to confirm those reports.

Santhi Soundarajan Media articles later reported that Santhi might have been born with an intersexed condition known as Androgen Insensitivity Syndrome. (AIS) Soundarajan won a silver medal in the women's 800 m race at the 2006 Asian Games held in Doha , Qatar [However, she underwent a sex test shortly afterwards, and the results indicated that she "does not possess the sexual characteristics of a woman. Soon after the results of the sex test came out, she was stripped of her silver medal].

In September 2007, Soundarajan was reported to have attempted suicide Two months later, Soundarajan took up coaching, starting a training academy at her home district of Pudukkottai, and became an athletics coach with the regional government. By 2009, her academy had 68 students and her students had won the first and third [10]. marathon Chennai positions in the