Inheritance

Dr. Zeyad Akawi Jreisat, M.D., M.A., Ph.D.

AUG

Intro n

Exon Transcription

TAA

mRNA
Translation

Protein

Chromosomal Theory of Inheritance

Chromosomes contain the genetic material that is transmitted from cell to cell and from parent to offspring Chromosomes are replicated and passed along generation after generation from parent to offspring. The nuclei of most eukaryotic cells contain chromosomes that are found in homologous pairs. During gamete formation, different types of chromosomes segregate independently of each other. Each parent contributes one set of chromosomes to its offspring.

Types of Inheritance
- Mendelian
- Autosomal dominant - Autosomal recessive - X-linked recessive - X-linked dominant - Nontraditional - Mitochondrial - Imprinting - Uniparental disomy - Mosaicism - Multi-factorial

Symbols for Pedigrees

Symbols for Pedigrees

 Pedigree: Expression of segregation or transmission of

traits within families.

Proband or index case: 1st family member seeking

medical attention (P).

Generation: Roman numbers (I, II, etc.). Individuals: Arabic numbers (1,2, etc.). Age: Next or below the symbol.

In order to understand Mendalian inheritance, several essential terms must first be defined

 Locus: A specific position on a chromosome. Alleles: alternative forms of a gene, or of a DNA

sequence, at a given locus.

Homozygous: both alleles at a locus are identical. Heterozygous: both alleles at a locus are different. A compound heterozygote: two different mutant
alleles at a given locus.

Double heterozygote: One mutant allele at each of two

different loci.

 Genotype: the genetic constitution or composition of an

individual.

Phenotype: the observed results of the interaction of the

genotype with environmental factors.

Genotype & Phenotype: are a musical analogy. Mendelian diseases: the result of a single mutant gene
that has a large effect on phenotype, inherited in a simple patterns.

Autosomal diseases: Encoded by genes on one of the

22 pairs of autosomes (non-sex chromosomes).

X-linked: encoded by a mutant gene on the X

chromosome.

A Comparison of Homologous Chromosomes

or

N Ab

Ab

Ab

Ab1

Ab2

Homozygous: Both alleles at a locus are the same.

Heterozygous: At the locus one gene is the wild type and the other mutant.

Compound heterozygote: Both allele are abnormal but different variations.

Mendelian genetics
Principle of segregation: Sexually reproducing organisms possess genes that occur in pairs and that only one member of this pair is transmitted to the offspring

Principle of independent assortment: genes at different loci are transmitted independently. In a reproductive event, a parent transmits one allele from each locus to its offspring and the allele transmitted at one locus has no effect on which allele is transmitted at the other locus

What is a trait?
Widows peak

ww

WW or Ww

How do we inherit a single trait?

We have to know the mode of inheritance
Dominant allele It is expressed when present It is designated with a capital (uppercase) letter An example is W for widows peak.

Recessive allele It is only expressed in the absence of a dominant allele. It is designated with a lowercase letter indicates An example is w for continuous hairline.

Proper use of the Punnett Square

A Punnett square can then be used to determine the phenotypic ratio among the offspring The punnett square can be used when it is hard to imagine the phenotypic ratio from any cross (i.e. Yy X Yy). Single gene: Yy X Yy = 3:1 Two genes: YyZz X YyZz = 9:3:3:1

Basic concepts of Probability

Laws of probability alone can be used to determine results of a cross. The laws are: Multiplication rule: the probability that two or more independent events will occur together is the product of their chances occurring separately. Addition rule: the chance that an event that can occur in two or more independent ways is the sum of the individual chances.

In the cross of Ww x Ww, what is the chance of obtaining either a W or a w from a parent?
Chance of W = , or chance of w = The probability of these genotypes is: The chance of WW = x = The chance of Ww = x = The chance of wW = x = The chance of ww = x = The chance of widows peak (WW, Ww, wW) is + + = or 75%.

Genotype versus Phenotype

Genotype refers to the genes of an individual which can be represented by two letters. Homozygous means that both alleles are the same; for example, WW stands for homozygous dominant ww stands for homozygous recessive.

Heterozygous means that the members of the allelic pair are different for example, Ww, a heterozygote

Genotype versus Phenotype

Phenotype refers to the physical or observable characteristics of the individual. Both WW and Ww result in widows peak, the phenotype is a widow's peak however, we have two genotypes resulting in the same phenotype. ww results in a straight hairline in this case, the phenotype can only result from one genotype

Genotype and gene frequency

The prevalence of many genetic diseases varies considerably from one population to another. The variation is due to the difference in proportion genotypes and alleles in a population.

Under simple conditions these frequencies can be estimated by direct counting. (MM: 64, MN: 120 and NN: 16) Total 200 subjects Genotype frequency = Genotype count/Total MM = 0.32; MN = 0.60; NN = 0.08 and the sum equal 1.

Gene (Allele) frequencies are easily estimated from genotype frequencies

How were allele frequencies estimated ? For Eskimo - Freq .of M = (0.835 + (0.5 x 0.156 )) = .913 Freq. of N = (0.009 + .(0.5 x 0.156 )) = .087

Example
Imagine that we have typed 200 individuals in a population for MN blood group, of these we have 64 with MM genotype, 120 with MN genotype and 16 with NN genotype. What is the genotype frequency? It is obtained simply by dividing each genotype count by the total number of subjects, for MM genotype it is 64/200 = 0.32 for MN genotype is 120/200 = 0.6 and for NN genotype is 16/200 = 0.08 the sum of these frequencies must equal 1

 What is the gene frequency? The gene frequency for each allele, M and N can be obtained by the process of gene counting. For M, each MM homozygous has two M alleles while each MN heterozygous has one allele therefore, the number of genes is (64 X 2) + 120 = 284 genes For N, each NN homozygous has two N alleles while each MN heterozygous has one allele therefore, the number of genes is (16 X 2) + 120 = 152 genes in total there are 400 genes at the MN locus To obtained the frequency of M, we divide the number of M allele by the total number of alleles at that locus 248/400 = 0.62 The same for the N allele, 152/400 = 0.38 The sum of the two frequencies must equal 1

Classification of genetic disorders

Single-gene disorders Chromosome disorders Multifactorial disorders

Single-gene disorders
Caused by mutations in individual genes. Mutations may be present in only one or both copies of a gene. Usually exhibit obvious and characteristic pedigree patterns.

Affect 2% of population sometime over an entire life span.

 Many important and well-understood genetic diseases are the result of a mutation in a single gene.
Single-gene or monogenic traits are also known as Mendelian traits. The variation in traits is caused by the presence of different alleles at individual loci Mendels key contributions to genetics were The principles of segregation Independent assortment The effects of one allele may mask those of another (dominance and recessiveness)