Cytogenetics Overview

A set of flashcards covering key concepts in cytogenetics, focusing on chromosome structure, types, and functions.

Cytogenetics

The study of chromosomes and their structure, function, and behavior.

Chromosome complement

The total number of chromosomes in a cell.

Normal human chromosome complement

46 chromosomes (23 matching pairs).

Homologous chromosomes

Chromosomes that have the same morphology.

Non-homologous chromosomes

Chromosomes that differ morphologically.

Centromere

The constriction point in each chromosome that separates it into two arms.

Short arm

The 'p' arm of a chromosome.

Long arm

The 'q' arm of a chromosome.

Telomeres

End structures of chromosomes that ensure their integrity during cell division.

Autosomal Chromosomes are classically distinguishable based on

1. Size - There is an inverse relationship between the number of assigned to the chromosome and the size of chromosomes. The smaller the number, the bigger the chromosome. Biggest is number 1.

2. Centromere Position - the centromere may be located in the middle (metacentric), off-center (submetacentric), or near one end (acrocentric).

3. Banding Pattern - Differential staining along the chromosome depends on the composition of the DNA on chromatic structure.

Centromere position

The location of the centromere on a chromosome affecting its shape.

Metacentric

Chromosomes with a centrally located centromere and equal-length arms.

Submetacentric

Chromosomes with a centromere located slightly off center, resulting in arms of unequal length.

Acrocentric

Chromosomes with the centromere near one end, creating a long arm and a very short arm.

Euchromatin

A lightly packed form of chromatin that is associated with actively expressed genes. Euchromatin is typically more accessible for transcription compared to heterochromatin.

Heterochromatin

Condensed chromatin that is usually not transcribed.

Light histological staining

Indicates regions of the chromosome that are less condensed, associated with gene activity.

Always condensed during metaphase/mitosis

Refers to the state of chromatin during cell division when it is most visible.

XIC

X-Inactivation Center: A region on the X chromosome that is involved in the process of X-inactivation, ensuring dosage compensation between males and females.

XIST

A gene located within the X-inactivation center (XIC) that produces a long non-coding RNA crucial for the process of X-inactivation in female mammals.

Sister chromatids

replicated forms of a chromosome joined together by the centromere and eventually separated during mitosis

The three stages of the Y chromosome evolutionary diversion

1. Acquisition of the testis determining gene - the first step in X-Y differentiation was the acquisition of a testis-determining gene by the proto-Y chromosome

2. Inversion - a series of large-scale inversions, most likely on the Y chromosome, suppressed recombination between X and Y. Throughout this process, X chromosome retained a partner for crossing over but the Y’s crossing over opportunities became limited.

3. Deletion - over the course of evolution, the X chromosome retained many of its ancestral genes, but the Y chromosome lost many of its regions and retains only 3%

Most parts of X and Y chromosomes are non-homologous

While most of the X and Y chromosome are non-homologous, there are 2 regions located at the distal end of both long and short arms, the Pseudoautosomal Regions (PAR) the PAR regions contain inherited genetic sequences that are carried in both the X and Y chromosomes.

X and Y Chromosomes during Meiosis

The X and Y chromosomes undergo independent assortment during meiosis, with homologous chromosomes pairing and exchanging genetic material via recombination specifically in the pseudoautosomal regions while remaining mostly non-homologous.

The Y Chromosome

• a gene-poor chromosome, containing approximately 45-50 male-specific genes. These genes are related to sexual differentiation, the development of sexual characteristics, and spermatogenesis.

  • Contains the SRY locus (Sex-determining Region of the Y) which plays a role in sex determination during development, encoding transcription factors that directly affect the differentiation of male gonads.

Sex determination in human embryos

1. Sex determination begins at fertilization - early in development, by genetics, the sex chromosome complement of the developing embryo is XX or XY

2. Molecular Stage - at the molecular level, molecular expression of transcription factors promotes the initiation and differentiation of the testis and ovaries. The critical decision depends on a titration of SRY against DAX1.

3. Development of the male and female sexual characteristics- hormone production, hormonal mediated development

DAX1 vs. SRY

Both are critical for sex determination, with SRY promoting testis formation and DAX1 antagonizing its effects to promote ovarian development.

Sex chromosome and sex reversal

in humans, sex reversal can occur due to 

1. Due to the mutation in the SRY causing dysregulation of gene expression

2. This can happen due to Translocation of the SRY region, leaving the Y-Chromosome missing the SRY region. 

SRY XX males

are individuals who have a male phenotype but exhibit an XX chromosomal pattern due to mutations or translocation affecting the SRY gene.

SRY^- XY females

are individuals with a female phenotype but possess XY chromosomes, often due to mutations in the SRY gene that disrupt normal male sex development.

the X Chromosome

spans about 155 million DNA base pairs and represents approximately 5% of the total DNA in cells 

It is estimated there are 1000 genes on the X chromosome

In addition to genes involved in sexual differentiation, 27% of genes linked to mental retardation were mapped on the X Chromosome, suggesting X-linked genes play a disproportionate role in the development of human intelligence.

What is X-inactivation?

X-inactivation is the process by which one of the two X chromosomes in female mammals is randomly inactivated during early embryonic development, leading to dosage compensation of X-linked genes between males and females.

Barr Body

a condensed, inactivated X chromosome found in female mammals, typically forming heterochromatin to achieve dosage compensation.

X Inactivation Center

is a DNA coding area that is part of each X chromosome. The XIC is necessary for X inactivation.

• within the XIC there are many RNA-coding sequences that are necessary for X-chromosome inactivation

• Rnf12 coding gene (locus) is located upstream of XIC

• The Rnf12 protein regulates transcription

• The cell uses the levels of Rnf12 as a molecular sensor

  • Threshold level of Rnf-12 is required to trigger X inactivation

the role of XIST

X-Inactive Specific Transcript (XIST) is an RNA molecule that coats the inactive X chromosome, promoting its silencing and facilitating the formation of the Barr body, which is crucial for X-inactivation.

• XIST expression is the first detectable event in x inactivation, and it remains in the nucleus 

• Rnf12 regulates the transcription of XIST

  • Only expressed in the X chromosome that will become the inactive X 

Heritability and Gene Transmission

refers to the proportion of observed variation in a trait that can be attributed to inherited genetic factors, influencing how traits and genetic conditions are passed from one generation to the next.

meiosis vs. mitosis

Meiosis is a type of cell division that reduces the chromosome number by half, producing four genetically diverse gametes, while mitosis is a process of cell division that results in two genetically identical daughter cells with the same number of chromosomes as the parent cell.

three unique features of meiosis

1. Synapses

2. Reduction division

3. Random assortment of chromosomes cross-over or homologous recombination of chromosomes, and genetic variation

Synapses

occur when homologous chromosomes pair up during meiosis, allowing for genetic exchange and recombination.

random assortment

of chromosomes during meiosis refers to the process by which different combinations of maternal and paternal chromosomes are distributed to gametes, increasing genetic diversity.

crossing over between the duplicated maternal and paternal chromosomes during meiosis

is the process in which homologous chromosomes exchange genetic material, resulting in new combinations of alleles and increased genetic variation in gametes.

gametogenesis

the process by which gametes are produced through meiosis and cellular differentiation, leading to the formation of eggs and sperm.

• during gametogenesis, the chromosome number is reduced by half & the morphology of the cells is altered

• In both genders, the process results in the production of highly specialized sex cells that are prepared for fertilization

  • The process in males is called spermatogenesis, and in females is called oogenesis. 

Spermatogenesis 

is the process of sperm cell development in males, involving meiosis and subsequent maturation to produce functional sperm from spermatogonia.

• occurs in the testis

• Spermatogonia divide by mitosis from puberty until death to produce daughter cells, primary spermatocytes

• Spermatocytes undergo meiosis to produce haploid cells, known as spermatic, which develop into mature sperm.

  • Begins at puberty, and continues throughout the males life 

Oogenesis

is the process of egg cell development in females, involving meiosis and maturation, to produce functional ova from oogonia. It typically results in the formation of a single mature egg and polar bodies, and begins before birth but completes during the menstrual cycle.

• Oogenesis occurs in the ovary and involves multiple stages, including the growth and maturation of primary follicles, which eventually lead to ovulation and the release of a mature ovum.

• All primary oocytes begin meiosis during embryonic development and then arrest at the first meiotic division, meiosis I. They remain in meiosis I until puberty.