GENETICS Dr. Samar Saleh Assiss. Lecturer Mosul Medical College Pathology3 rd year

Genetics is the study of single or a few genes and their phenotypic effects. G enomics is the study of all the genes in the genome and their interactions. The two most common forms of DNA variations in the human genome are single-nucleotide polymorphisms (SNPs) and copy number variations (CNVs).

Genes and Human Diseases It was found about 50% of spontaneous abortion during early pregnancy due to chromosomal abnormalities. Human genetic disorders can be broadly classified into: Disorders related to mutations in single genes with large effects, these associated with highly penetrate, meaning that the presence of the mutation is associated with the disease in a large proportion of individuals.

they usually follow the classic Mendelian pattern of inheritance (e.g. sickle cell anemia) Chromosomal disorders. These arise from structural or numerical alteration in the autosomes and sex chromosomes, they are uncommon but associated with high penetrance.

Complex multigenic disorders more common than the previous two. They are caused by interactions between multiple variant forms of genes and environmental factors. including atherosclerosis, diabetes mellitus, hypertension, and autoimmune diseases.

MUTATIONS is defined as a permanent change in the DNA malformations. Somatic cells Germ cells cancers & inh inherited disease congenital abnormalities Mutation

Point mutations within coding sequences alter the code in a triplet of bases and lead to the replacement of one amino acid by another in the gene product. termed missense mutations ( if the replaced amino acid cause little change conservative,while if lead to very different amino acid non conservative) Example : Sickle cell anemia replacement glutamic acid in β- gloin chain of Hb by valine ( CTC CAC) on DNA (GAG GUG) on mRNA

Non sense mutation : a point mutation affecting the codon for glutamine (CAG) creates a stop codon (UAG) if U is substituted for C premature termination of β-globin gene translation( β 0 -thalassemia )

Mutations within non coding sequences Point mutations or deletions involving the regulatory sequences in DNA (promoter & the inhancer) that involve in DNA transcription interferes with normal processing of the initial mRNA transcripts failure to form mature mRNA. the gene product is not synthesized.

Trinucleotide-repeat mutations amplification of a sequence of three nucleotides. Example fragile-X syndrome repeats of the sequence CGG within a gene called familial mental retardation 1 (FMR1).

Mendelian Disorders All mendelian disorders are the result of mutations in single genes that have large effects 80% to 85% of these mutations are familial autosomal mutations produce partial expression in the heterozygote and full expression in the homozygote Sickle cell anemia & sickle cell trait codominance. both of the alleles of a gene pair contribute to the phenotype. Histocompatibility and blood group antigens are good examples of codominant inheritance.

TRANSMISSION PATTERNS OF SINGLE-GENE DISORDERS three patterns of inheritance: autosomal dominant, autosomal recessive, and X-linked. Autosomal Dominant Disorders autosomal dominant conditions are characterized by the following: With every autosomal dominant disorder, some proportion of patients do not have affected parents

Clinical features can be modified by variations in penetrance and expressivity incomplete penetrance : individuals inherit the mutant gene but are phenotypically normal variable expressivity :if a trait is seen in all individuals carrying the mutant gene but is expressed differently among individuals’ Example :neurofibromatosis type 1, Sickle cell anemia In many conditions the age at onset is delayed: symptoms and signs may not appear until adulthood (as in Huntington disease).