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Basics of human genetics

Last updated: October 9, 2019


Human genetics is the study of the human genome and how genes are transmitted through generations. The human genome consists of 23 pairs of chromosomes (22 pairs of homologous chromosomes and one pair of sex chromosomes), each containing genes that code for proteins within the cell. On all homologous chromosome pairs, there are two forms of the same gene that are known as alleles, which are passed on from parent to offspring. Hereditary diseases are also passed down from parent to offspring via different patterns of inheritance, such as autosomal dominant, autosomal recessive, X-linked, and mitochondrial inheritance. These diseases often result from alterations within an individual's genes called mutations. Although some mutations are benign, many cause cellular dysfunction that manifests as disease. Understanding the mechanisms underlying the transmission of genetic material is vital for understanding and treating diseases that have a genetic component.

Basic concepts of genetics


For molecular structure of DNA and chromosomes, see nucleotides, DNA, and RNA.


The chromosomes are only visible during cell division, especially in metaphase.

Characteristics of chromosomes (chromosome morphology)

Chromosomes are classified based on their length, position of the centromere, and pattern of the bands!

For information on genetic testing, see chromosome testing in laboratory methods.

Traits, their genetic basis, and manifestations

Individuals, family, and population


Types of mutations

Mutations are alterations in the genome of a cell. They can occur as a result of errors during DNA replication or cell division as well as ineffective DNA repair mechanisms. Damage to DNA caused by endogenous and exogenous toxins can also lead to gene and chromosome mutations.

Mutations according to the affected cell population

Based on the affected cells, mutations can be classified as follows:

  • Germline mutation: (gametic mutation): mutations in the cells from which egg or sperm cells develop. These mutations can, therefore, be passed on to offspring
  • Somatic mutation: acquired mutations that are present only in certain somatic cells
  • Mosaicism: the presence of two or more populations of cells within an organism, each with different genomes
    • Chromosomal mosaicism: cell populations with different karyotypes are present in one organism.
      • Example: : In Turner syndrome, sex chromosome mosaicism is frequently present (one population of X0 cells, one population of XX cells).
    • Gonadal mosaicism: only some germ cells of an individual carry a mutation
      • Caused by a mutation in the genome of a primordial germ cell during mitosis in germline development
      • If other people in the family (parents and other relatives) do not have the disorder, suspect this type of mosaicism.
    • Somatic mosaicism: only some of the individual's somatic cells carry a mutation
    • Chimerism: the presence of two genetically distinct cell lines in one individual that originate from two different zygotes; occurs, e.g., when linked oocytes are fertilized.
  • Chromosomal instability: caused by mutations in genes that are responsible for DNA repair
  • Two-hit hypothesis: If a mutation is present in one allele of a tumor suppressor gene and the other allele is deactivated by a second mutation, the cell becomes a tumor cell.
  • Loss of heterozygosity: (LoH): loss of one allele of a gene after inactivation of the other gene by a mutation

Chromosomal aberrations

Chromosomal aberrations are mutations affecting large segments of DNA. They may be visible on karyogram.

Uniparental disomy cannot be detected via karyotyping because the number of chromosomes is normal with no loss of genetic material!

HeterodIsomy = meiosis I error; IsodIsomy = meiosis II error.

Gene mutations

Nonsense and frameshift mutations usually change the fundamental structure of the coded protein. For this reason, they typically lead to more severe disease manifestations than missense and silent mutations!

STOP the NONSENSE - NONSENSE mutation creates early STOP codons in the RNA.

Epigenetic regulation of gene expression

Epigenetics focuses on the heritable chemical modifications of DNA and histone proteins caused by environmental factors. Through these modifications, gene activity can be regulated, i.e., genes can be switched on or off. In contrast to genetic studies, epigenetics is not concerned with the information encoded in the DNA sequence itself.

Main epigenetic mechanisms of the regulation of gene activity

The epigenetic regulation of genes is all about whether or not genes are transcribed; . Classical genetics, on the other hand, is concerned with the presence or absence of a gene. Gene expression or repression is determined by chemical modifications of bases (methylation) and histone proteins (various covalent modifications), which are carried out by specialized enzymes.

Epigenetics is concerned with the investigation of external factors that activate or deactivate genes and therefore control transcription!

DNA methylation inhibits transcription; histone methylation can inhibit or enhance transcription!

Typical epigenetic processes


Pedigree analysis

Pedigree analysis allows the inheritance patterns of certain traits to be identified. It may, for example, detect evidence of autosomal dominant inherited disorders. In addition to clinical features, an affected gene can be investigated for a mutation or the affected gene's karyotype can be determined.

  • Definition: depiction of family relationships with special emphasis on certain phenotypical traits of individual family members
  • Aim: to draw conclusions from the phenotype to the genotype of family members and to determine patterns of inheritance
  • Form:
    • Symbols indicate individual family members.
    • Lines between the symbols show the degree of the relationship.
    • Generations are indicated with Roman numerals.
    • The children of a generation are designated with Arabic numerals in their order of birth.
    • Affected family members, i.e., carriers, are represented by colored symbols.
  • Questions in pedigree analysis:
    1. Dominant or recessive inheritance?
      • Question 1: Does every affected family member have a parent that is also affected?
        • Yes → dominant inheritance of the trait
        • No → recessive inheritance of the trait
    2. Autosomal or gonosomal inheritance?
      • Question 2: Are male family members mainly affected?
        • Yes → (most likely) X-linked recessive inheritance
      • Question 3: If the following criteria are met, the disease (most likely) follows an X-linked dominant pattern of inheritance:
        • Do all affected males also have an affected mother?
        • Do all affected males have healthy sons?
        • Does no affected male have a healthy daughter?
      • If one of these criteria are not met and question 1 has been answered in the affirmative, the disorder is most likely autosomal dominant. If question 1 is answered with a negative response, the disorder is most likely autosomal recessive.

Autosomal dominant inheritance

An autosomal dominant disease with complete penetrance will always manifest in each generation!

Autosomal recessive inheritance

Heterozygote mother
v (altered allele) N (normal allele)
Heterozygote father v (altered allele) vv child with disease Nv carrier
N (normal allele) vN carrier NN healthy child

X-linked recessive inheritance

Heterozygote mother (carrier)
x (altered allele) X (normal allele)
Healthy father X Xx carrier XX healthy daughter
Y xY diseased son XY healthy son

In X-linked recessive inheritance, all male offspring of the affected father (and a healthy mother) are healthy, do not carry the altered allele, and therefore cannot pass on the altered allele!

X-linked dominant inheritance

Heterozygote mother (diseased)
X (altered allele) x (normal allele)
Healthy father xX Xx diseased daughter xx healthy daughter
Y XY diseased son xY healthy son
Heterozygote father (diseased)
X (altered allele) Y (normal allele)
Healthy mother x Xx diseased daughter xY healthy son
x Xx diseased daughter xY healthy son

Mitochondrial inheritance

Polygenic inheritance

Heterozygote frequency


Multifactorial inheritance disorders

  • Definition: disorders that are influenced by various factors (e.g., genetics, external influences like lifestyle and environment)
    • Frequency: Most diseases are caused by multiple factors.
  • Index case: first person within a family to manifest with the disease
  • Threshold effect: effect observed in some multifactorial diseases → the disease only develops when genetic predispositions and external factors combine to reach a certain threshold value
  • Gene-environment interaction: Genetic predisposition affects susceptibility to environmental factors.
    • Example: Children exposed to physical or mental abuse that also carry a certain genetic disposition (defect in monoamine oxidase A) are at especially high risk of developing antisocial behavior.


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