THE ROLE OF GENETICS IN MEDICINE & Chromosomal Basis of Heredity Dr S.M.B.Tabei

THE ROLE OF GENETICS IN MEDICIN 1- Genetics as a Medical Specialty

Relevance of Genetics to All Medical Practice

Disciplines within Human and Medical Genetics Human genetics, Human genetics: is the science of variation and heredity in human beings, Medical genetics : Medical genetics :deals with the subset of human genetic variation that is of significance in the practice of medicine and in medical research. Within human and medical genetics, there are many fields of interest : 1- cytogenetics 2- molecular and biochemical genetics 3- genomics 4- population genetics 5- developmental genetics 5- clinical genetics 6- Genetic counseling

CLASSIFICATION OF GENETIC DISORDERS genetic variation and mutation in the etiology of a large number of disorders Three main types of disorders are recognized: 1- Single gene disorders : Caused by individual mutant genes. may be present on only one chromosome or on both chromosomes. 2- Chromosome disorders : 2- Chromosome disorders : an excess or a deficiency of the genes contained in whole chromosomes or chromosome segments. 3- Multifactorial disorders : 3- Multifactorial disorders : Multifactorial inheritance is responsible for a number of developmental disorders resulting in congenital malformations and for many common disorders of adult life

Chromosomal Basis of Heredity

THE HUMAN CHROMOSOMES

The classification of chromosomes by the position of the centromere. A telocentric chromosome has its centromere at one end; when the chromosome moves toward one pole of the cell during the anaphase of cellular division, it appears as a simple rod. An acrocentric chromosome has its centromere somewhere between the end and the middle of the chromosome; during anaphase movement, the chromosome appears as a J. A metacentric chromosome has its centromere in the middle and appears as a V during anaphase. The classification of chromosomes by the position of the centromere. A telocentric chromosome has its centromere at one end; when the chromosome moves toward one pole of the cell during the anaphase of cellular division, it appears as a simple rod. An acrocentric chromosome has its centromere somewhere between the end and the middle of the chromosome; during anaphase movement, the chromosome appears as a J. A metacentric chromosome has its centromere in the middle and appears as a V during anaphase. (d) Sub metacentric P q

Banding pattern of human chromosomes

THE LIFE CYCLE OF A SOMATIC CELL Phases of the cell cycle The division cycle of most eukaryotic cells is divided into four discrete phases: M, G1, S and G2. M phase (mitosis) is usually followed by cytokinesis. S phase is the period during which DNA replication occurs. The cell grows throughout interphase, which includes G1, S and G2.The relative lengths of the cell cycle phases shown here are typical of rapidly replicating mammalian cells. Phases of the cell cycle : The division cycle of most eukaryotic cells is divided into four discrete phases: M, G1, S and G2. M phase (mitosis) is usually followed by cytokinesis. S phase is the period during which DNA replication occurs. The cell grows throughout interphase, which includes G1, S and G2.The relative lengths of the cell cycle phases shown here are typical of rapidly replicating mammalian cells.

Cell cycle checkpoints Several checkpoints function to ensure that complete genomes are transmitted to daughter cells. One major checkpoint arrests cells in G2 in response to damaged or unreplicated DNA. The presence of damaged DNA also leads to cell cycle arrest at a checkpoint in G1. Another checkpoint, in M phase, arrests mitosis if the daughter chromosomes are not properly aligned on the mitotic spindle. if the damage is excessive, until the cell is instructed to die by programmed cell death (a process called apoptosis).

Replication of chromosomes  Replication is the process of duplicating a chromosome Occurs prior to division Replicated copies are called sister chromatids Held together at centromere

Mitosis Five stages of mitosis: 1- Prophase 2- Prometaphase 3- Metaphase 4- Anaphase 5-Telophase

Prophase  - Replicated chromosomes condense.  - the beginning of the formation of the mitotic spindle.  - Microtubules organize (centrosomes )into a spindle  - The centrosomes gradually move to take up positions at the poles of the cell

Prometaphase -- nuclear membrane breaks up -- allowing the chromosomes to disperse within the cell and to attach -, via their kinetochores, to microtubules of the mitotic spindle -- The chromosomes begin to move toward a point midway between - the spindle poles, a process called congression

Metaphase  - Chromosomes line up on the metaphase plate.  - the chromosomes reach maximal condensation.  - Spindle microtubules are attached to centromeres of chromosomes.

Anaphase  - Centromeres of sister chromatids of each chromosome separate  - Chromosomes move to opposite ends of the cell

Telophase  Nuclear membranes form  Spindle disappears  Division of cytoplasm occurs (cytokinesis)

Cytokinesis Cytoplasmic division occurs after nuclear division is complete. Two cells are formed.

The Human Karyotype

MEIOSIS - Meiosis is the type of cell division by which the diploid cells of the germline ( primary spermatocytes or primary oocytes, ) give rise to haploid gametes. -Meiosis consists of one round of DNA synthesis followed by two rounds of chromosome segregation and cell division

The two successive meiotic divisions are called meiosis I and meiosis II Meiosis I is also known as the reduction division because it is the division in which the chromosome number is reduced from diploid to haploid in which the chromosome number is reduced from diploid to haploid In Meiosis I occur genetic recombination (also called meiotic crossing over) occurs. thus ensuring that none of the gametes produced by meiosis is not identical to another. MEIOSIS

The First Meiotic Division (Meiosis I) PROPHASE 1 The prophase of meiosis I is a complicated process that differs from mitotic prophase in a number of ways, with important genetic from mitotic prophase in a number of ways, with important geneticconsequences. Several stages are defined: 1- Leptotene. 2- Zygotene 3- Pachytene 4- Diplotene 5- Diakinesis

The chromosomes, replicated during the preceding S phase and beginning to condense. and beginning to condense. two sister chromatids of each chromosome are so closely aligned that they cannot be distinguished. aligned that they cannot be distinguished.

homologous chromosomes begin to pair closely along their entire length (synapsis ). DNA sequences into alignment along the length of the entire chromosome.

The chromosomes become much more tightly coiled. Synapsis is complete, Each pair of homologs appears as a bivalent (tetrad four chromatids) Crossing over takes place

the synaptonemal complex disappears, the two components of each bivalent now begin to separate from each other. Although the homologous chromosomes separate, each of their centromeres remains intact. Eventually the two homologs of each bivalent are held together only at points called chiasmata (crosses),

In this stage, the chromosomes reach maximal condensation.

Metaphase I begins, as in mitosis

Meiosis II Meiosis II

HUMAN GAMETOGENESIS AND FERTILIZATION Spermatogenesis

Oogenesis