Home > Articles

  • Print
  • + Share This
This chapter is from the book

How many disease genes are there?

In 1957, Victor McKusick was appointed director of the new Moore Clinic for Chronic Diseases at Johns Hopkins University and head of the newly established Division of Medical Genetics at its medical school.43 He had come into human genetics via his research on disorders affecting connective tissue, including Marfan's syndrome. Marfan's sufferers typically have long slender limbs and are often taller than normal. The most serious conditions associated with the disease primarily involve the cardiovascular system, as there may be leakage through the mitral or aortic valves that control blood flow through the heart. McKusick noticed that Marfan's syndrome exhibited a familial pattern of occurrence and, indeed, we know today that a dominant genetic mutation is involved. The Marfan's pedigree sparked McKusick's interest and he began to specialize in human clinical genetics.

In 1966, he published his first catalog of all known genes and genetic disorders, Mendelian Inheritance in Man (MIM). The 12th edition of his catalog was published in 1998. Meanwhile, a free online version (OMIM) first became available in 1987. It is continuously updated. The database is linked with the National Center for Biotechnology Information and the National Library of Medicine for distribution. In the 1980s, only a few genes were being found each year. By 2000, the number of genes discovered each year was approaching 175. More than 6,000 single gene disorders are currently known,44 meaning that mutations in somewhere around 24% of the approximately 25,000 human genes found so far can cause genetic disease. Because of the broad interest in disease genes as well as the availability of increasingly sophisticated technical and statistical tools, the rate of disease gene discovery has expanded rapidly. Whether or not it plateaus at some point remains to be seen.

It was originally thought that the human genome might contain as many as 100,000 genes. Once the Human Genome Project was completed in 2003 and a few further revisions were made, this number dropped to around 25,000, roughly the same range as the mouse (see Table 1–2). But the surprising thing is that these protein-encoding genes represent less than 2% of the 3.2 billion base pairs in the human genome.45 Unlike the even spacing of a string of pearls, our genes often cluster in gene-rich regions separated by gene-poor deserts.

Table 1–2. Genome sizes and gene density in humans as compared with other organisms frequently used in genetic research


Estimated size (base pairs)

Estimated gene number

Average gene density

Chromosome number

Homo sapiens (human)

3.2 billion


1 gene per 100,000 bases


Mus musculus (mouse)

2.6 billion


1 gene per 100,000 bases


Drosophila melanogaster (fruit fly)

137 million


1 gene per 9,000 bases


Arabidopsis thaliana (plant)

100 million


1 gene per 4,000 bases


Caenorhabditis elegans (roundworm)

97 million


1 gene per 5,000 bases


Saccharomyces cerevisiae (yeast)

12.1 million


1 gene per 2,000 bases


Escherichia coli (bacteria)

4.6 million


1 gene per 1,400 bases


H. influenzae (bacteria)

1.8 million


1 gene per 1,000 bases


From Human Genome Project Information: Functional and Comparative Genomics Fact Sheet. www.ornl.gov/sci/techresources/Human_Genome/faq/compgen.shtml

The human genome is distributed between 23 chromosomes. These are found singly in sperm and eggs (haploid), but in pairs in all of the rest of our cells (diploid). This halving in chromosomes number in eggs and sperm is achieved during the two cell divisions of meiosis. During the first division, homologous paternal and maternal chromosomes pair respectively with paternal and maternal chromosomes assorting independently of each other. During the pairing, chromosome segments are exchanged between homologs, a process called genetic recombination (see Glossary for a brief introduction to Mendelian genetics). Although not generating new genetic alterations, the processes of independent assortment and recombination provide the opportunity to assort existing parental genes in a variety of new combinations. Creation of all of this new genetic variability on which natural selection can act is a major reason why sexual reproduction predominates in animals and plants.

Like the genes of other higher organisms, human genes themselves are not single blocks of DNA that encode specific proteins. Instead, they are broken up into coding sequences (exons) and noncoding sequences (introns). Following the process of transcription, when the information in a gene is copied into a messenger RNA molecule, the intron sequences are spliced out of the message so only the coding sequences in the messenger RNA can be translated into protein sequence.

What is all that other DNA doing that has no obvious genetic function? We know that at least 50% of the genome, perhaps more, is made up of repeated sequences that do not encode human proteins and often no proteins at all. These repeats are of several kinds, but the most abundant are "mobile" genetic elements that make up roughly 43% of the mammalian genome.46 They either are or at one time were capable of movement from one site in the genome to another.

Transposons are the first group of mobile elements. They comprise around 3% of the genome. The name transposon evokes the word transposition and, indeed, these elements are capable of moving from one to another place in the genome. The easiest way to think about transposition is as a "cut-and-paste" process. One cuts out a word, or a group of words, in a text and then pastes those words into a specific place elsewhere in the text. The important difference between transposition and cutting and pasting is that, although transposition will take place only into its target DNA sequence, the element can be pasted into that sequence anywhere in the genome. An enzyme called a transposase encoded by the element catalyzes the transposition process. Hence, transposons are sometimes called jumping genes.

The second group includes several sets of elements of which three are the most abundant. The first are endogenous retroviruses. These are viruses whose genetic material is RNA. An enzyme called a reverse transcriptase encoded by the virus catalyzes synthesis of DNA copies of the viral RNA. These DNA copies are then inserted into the genome. The AIDS virus is the best-known retrovirus, but unlike AIDS, the retroviral fragments that inhabit our genomes today are, for the most part, the remains of ancient retroviruses that have lost their ability to become independent of the genome.

LINES (long interspersed nuclear elements) comprise the second group (see Glossary for a more complete discussion of LINES and SINES). They are retrotransposons. One way to think about a retrotransposon is as an odd sort of printing press. An RNA copy is transcribed from the retrotransposon DNA. In the case of LINES, translation of the RNA copy results in the production of two proteins. One of these proteins is essential for the transposition process. The second catalyzes synthesis of a DNA copy of the RNA and then makes a cut in a specific DNA sequence (e.g., TTTTAA/AAAATT for L1) in the genome where the newly made retrotransposon can insert. This method of reproduction has the potential for enormously amplifying the number of retrotransposons in the genome that can then home into their target sequences wherever they are in the genome.

There are several different kinds of LINE elements, but L1, which predominates in the human genome, has evolved along with the mammals over the past 160 million years or more. Expansion in the number of L1s in the genome was rapid, but appears to have slowed down about 25 million years ago. The 500,000 or so copies of L1 present today in the human genome amount to around 18% of its content. The intact L1 element is about 6,000 base pairs in length, but truncated versions are common. L1s are the only active transposons in the human genome today.

SINES (short interspersed nuclear DNA elements) are short DNA sequences of less than 500 base pairs. SINES do not encode any proteins and are not autonomous. They can only transpose with the aid of the two proteins made by active LINE elements. The most important SINES are the Alu elements.47 More than a million copies of these short DNA sequences are found in the human genome. They represent around 13% of the total DNA. Alu elements originated and coordinated their amplification with the radiation of the primates about 65 million years ago.

Because nobody is exactly sure why human and other animal and plant genomes contain so many repeated elements, they have sometimes been treated as irritants with regard to the real genes, gaining them epithets such as "junk DNA" and "selfish DNA." In a recent review, Goodier and Kazazian point out that a more sophisticated name "dark matter" is coming into vogue for these repeated elements, acknowledging the fact that we don't really understand whether they have an as-yet-to-be-discovered function. Goodier and Kazazian prefer to think of mobile elements as "dark energy."48 They are "a dynamic force that not only accelerates expansion but also helps set the warp and weft of genomes for better and for worse. Transposable elements arose as intracellular parasites that became domesticated."

Well not entirely. Transposition of these elements can disrupt gene function. In a 1998 paper in Nature, Kazazian and his colleagues reported two unrelated cases of hemophilia A for which there was no family history, suggesting that the mutations had arisen de novo.49 Each of them involved the insertion of L1 sequences into the F8 gene. So we end this chapter where we began it—with hemophilia. Transposon insertions have also been implicated in a wide spectrum of genetic diseases other than hemophilia.50

  • + Share This
  • 🔖 Save To Your Account

InformIT Promotional Mailings & Special Offers

I would like to receive exclusive offers and hear about products from InformIT and its family of brands. I can unsubscribe at any time.


Pearson Education, Inc., 221 River Street, Hoboken, New Jersey 07030, (Pearson) presents this site to provide information about products and services that can be purchased through this site.

This privacy notice provides an overview of our commitment to privacy and describes how we collect, protect, use and share personal information collected through this site. Please note that other Pearson websites and online products and services have their own separate privacy policies.

Collection and Use of Information

To conduct business and deliver products and services, Pearson collects and uses personal information in several ways in connection with this site, including:

Questions and Inquiries

For inquiries and questions, we collect the inquiry or question, together with name, contact details (email address, phone number and mailing address) and any other additional information voluntarily submitted to us through a Contact Us form or an email. We use this information to address the inquiry and respond to the question.

Online Store

For orders and purchases placed through our online store on this site, we collect order details, name, institution name and address (if applicable), email address, phone number, shipping and billing addresses, credit/debit card information, shipping options and any instructions. We use this information to complete transactions, fulfill orders, communicate with individuals placing orders or visiting the online store, and for related purposes.


Pearson may offer opportunities to provide feedback or participate in surveys, including surveys evaluating Pearson products, services or sites. Participation is voluntary. Pearson collects information requested in the survey questions and uses the information to evaluate, support, maintain and improve products, services or sites, develop new products and services, conduct educational research and for other purposes specified in the survey.

Contests and Drawings

Occasionally, we may sponsor a contest or drawing. Participation is optional. Pearson collects name, contact information and other information specified on the entry form for the contest or drawing to conduct the contest or drawing. Pearson may collect additional personal information from the winners of a contest or drawing in order to award the prize and for tax reporting purposes, as required by law.


If you have elected to receive email newsletters or promotional mailings and special offers but want to unsubscribe, simply email information@informit.com.

Service Announcements

On rare occasions it is necessary to send out a strictly service related announcement. For instance, if our service is temporarily suspended for maintenance we might send users an email. Generally, users may not opt-out of these communications, though they can deactivate their account information. However, these communications are not promotional in nature.

Customer Service

We communicate with users on a regular basis to provide requested services and in regard to issues relating to their account we reply via email or phone in accordance with the users' wishes when a user submits their information through our Contact Us form.

Other Collection and Use of Information

Application and System Logs

Pearson automatically collects log data to help ensure the delivery, availability and security of this site. Log data may include technical information about how a user or visitor connected to this site, such as browser type, type of computer/device, operating system, internet service provider and IP address. We use this information for support purposes and to monitor the health of the site, identify problems, improve service, detect unauthorized access and fraudulent activity, prevent and respond to security incidents and appropriately scale computing resources.

Web Analytics

Pearson may use third party web trend analytical services, including Google Analytics, to collect visitor information, such as IP addresses, browser types, referring pages, pages visited and time spent on a particular site. While these analytical services collect and report information on an anonymous basis, they may use cookies to gather web trend information. The information gathered may enable Pearson (but not the third party web trend services) to link information with application and system log data. Pearson uses this information for system administration and to identify problems, improve service, detect unauthorized access and fraudulent activity, prevent and respond to security incidents, appropriately scale computing resources and otherwise support and deliver this site and its services.

Cookies and Related Technologies

This site uses cookies and similar technologies to personalize content, measure traffic patterns, control security, track use and access of information on this site, and provide interest-based messages and advertising. Users can manage and block the use of cookies through their browser. Disabling or blocking certain cookies may limit the functionality of this site.

Do Not Track

This site currently does not respond to Do Not Track signals.


Pearson uses appropriate physical, administrative and technical security measures to protect personal information from unauthorized access, use and disclosure.


This site is not directed to children under the age of 13.


Pearson may send or direct marketing communications to users, provided that

  • Pearson will not use personal information collected or processed as a K-12 school service provider for the purpose of directed or targeted advertising.
  • Such marketing is consistent with applicable law and Pearson's legal obligations.
  • Pearson will not knowingly direct or send marketing communications to an individual who has expressed a preference not to receive marketing.
  • Where required by applicable law, express or implied consent to marketing exists and has not been withdrawn.

Pearson may provide personal information to a third party service provider on a restricted basis to provide marketing solely on behalf of Pearson or an affiliate or customer for whom Pearson is a service provider. Marketing preferences may be changed at any time.

Correcting/Updating Personal Information

If a user's personally identifiable information changes (such as your postal address or email address), we provide a way to correct or update that user's personal data provided to us. This can be done on the Account page. If a user no longer desires our service and desires to delete his or her account, please contact us at customer-service@informit.com and we will process the deletion of a user's account.


Users can always make an informed choice as to whether they should proceed with certain services offered by InformIT. If you choose to remove yourself from our mailing list(s) simply visit the following page and uncheck any communication you no longer want to receive: www.informit.com/u.aspx.

Sale of Personal Information

Pearson does not rent or sell personal information in exchange for any payment of money.

While Pearson does not sell personal information, as defined in Nevada law, Nevada residents may email a request for no sale of their personal information to NevadaDesignatedRequest@pearson.com.

Supplemental Privacy Statement for California Residents

California residents should read our Supplemental privacy statement for California residents in conjunction with this Privacy Notice. The Supplemental privacy statement for California residents explains Pearson's commitment to comply with California law and applies to personal information of California residents collected in connection with this site and the Services.

Sharing and Disclosure

Pearson may disclose personal information, as follows:

  • As required by law.
  • With the consent of the individual (or their parent, if the individual is a minor)
  • In response to a subpoena, court order or legal process, to the extent permitted or required by law
  • To protect the security and safety of individuals, data, assets and systems, consistent with applicable law
  • In connection the sale, joint venture or other transfer of some or all of its company or assets, subject to the provisions of this Privacy Notice
  • To investigate or address actual or suspected fraud or other illegal activities
  • To exercise its legal rights, including enforcement of the Terms of Use for this site or another contract
  • To affiliated Pearson companies and other companies and organizations who perform work for Pearson and are obligated to protect the privacy of personal information consistent with this Privacy Notice
  • To a school, organization, company or government agency, where Pearson collects or processes the personal information in a school setting or on behalf of such organization, company or government agency.


This web site contains links to other sites. Please be aware that we are not responsible for the privacy practices of such other sites. We encourage our users to be aware when they leave our site and to read the privacy statements of each and every web site that collects Personal Information. This privacy statement applies solely to information collected by this web site.

Requests and Contact

Please contact us about this Privacy Notice or if you have any requests or questions relating to the privacy of your personal information.

Changes to this Privacy Notice

We may revise this Privacy Notice through an updated posting. We will identify the effective date of the revision in the posting. Often, updates are made to provide greater clarity or to comply with changes in regulatory requirements. If the updates involve material changes to the collection, protection, use or disclosure of Personal Information, Pearson will provide notice of the change through a conspicuous notice on this site or other appropriate way. Continued use of the site after the effective date of a posted revision evidences acceptance. Please contact us if you have questions or concerns about the Privacy Notice or any objection to any revisions.

Last Update: November 17, 2020