Genetics Terms Starting With L
Genetics Glossary: L
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Leber's Congenital Amaurosis
/ LEE-berz kon-JEN-ih-tul am-aw-ROH-sis / · Named for Theodor Leber (1869) + Latin: congenitus + Greek: amaurosis (darkening)
Leber's Congenital Amaurosis is a group of severe inherited retinal dystrophies caused by mutations in genes required for photoreceptor function, resulting in profound visual impairment from birth or early infancy.
LCA is caused by mutations in at least 20 different genes involved in phototransduction, retinal development, and photoreceptor maintenance. The most common form, LCA2, results from mutations in the RPE65 gene, which encodes an enzyme required for vitamin A recycling in the retinal pigment epithelium. LCA affects roughly 2 to 3 per 100,000 births and is the most common cause of inherited blindness in children.
Inheritance is autosomal recessive in most forms, meaning both copies of the affected gene must carry mutations for the disease to appear.
Voretigene neparvovec, approved by the FDA in 2017, was the first gene therapy for an inherited disease cleared in the United States; it treats LCA2 by delivering a functional RPE65 gene via adeno-associated virus injected beneath the retina.
Are Enzymes Proteins? →LCA is not a single disease. It is a clinically and genetically heterogeneous group of disorders caused by mutations in many different genes, each potentially requiring a distinct therapeutic approach.
Patients with LCA2 treated by subretinal injection of AAV-RPE65 in clinical trials led by Jean Bennett and Albert Maguire at the University of Pennsylvania reported navigating obstacle courses and reading standard print for the first time. The treatment benefits only patients whose disease stems from biallelic RPE65 mutations, which account for roughly 6 percent of all LCA cases.
Lethal Allele
/ LEE-thul uh-LEEL / · Greek: lethe (oblivion) + allelon (of one another)
Lethal Allele is an allele that causes the death of an organism when present in the homozygous or hemizygous state, usually by disrupting a process required for development or survival.
Recessive lethal alleles are tolerated in heterozygous carriers but cause death when homozygous, often during embryonic development. Their presence distorts expected Mendelian ratios because the homozygous lethal class is absent from offspring. The yellow coat color allele in mice is a classic example: heterozygotes are yellow, but homozygotes die in utero because the same allele disrupts the Agouti signaling gene, which is required for normal development.
About 30 percent of all spontaneous miscarriages in humans are estimated to result from embryos homozygous for lethal alleles or carrying chromosomal abnormalities incompatible with development.
A lethal allele does not always kill immediately at conception. Some lethal alleles cause death only at specific developmental stages or under particular environmental conditions, and others reduce fitness to near zero without causing rapid death.
Top Bioethical Issues →The yellow agouti allele in house mice (Mus musculus) is pleiotropic: heterozygotes survive and display yellow fur, but homozygotes die before implantation because the allele also disrupts expression of a neighboring gene required for early embryogenesis. Crosses between two yellow mice therefore produce yellow and wild-type offspring in a 2-to-1 ratio rather than the 3-to-1 ratio expected for a simple dominant trait.
LINE
/ LYN / · Abbreviation: Long Interspersed Nuclear Element
LINE is a class of long retrotransposable elements that make up a significant fraction of mammalian genomes and can copy and reinsert themselves into new genomic locations through an RNA intermediate.
LINEs encode their own reverse transcriptase and endonuclease, enabling autonomous retrotransposition in which the element is transcribed into RNA, reverse transcribed into DNA, and inserted at a new genomic site. Human LINE-1 elements make up about 17 percent of the human genome, representing the largest single class of repetitive DNA. Although most LINEs are inactive because of accumulated mutations, a small number remain capable of transposition and can cause disease by inserting into gene coding or regulatory sequences.
At least 100 human genetic diseases have been linked to LINE-1 insertions disrupting specific genes.
LINE-1 retrotransposition in somatic cells has been detected in neurons and in many cancer types, suggesting that mobile element activity continues throughout an individual's lifetime and may contribute to genomic variation among cells of the same brain.
Fun Facts About the Nervous System →LINEs are not simply junk DNA. Many LINE-derived sequences have been co-opted by the genome to contribute enhancers, promoters, and non-coding RNA genes that regulate nearby genes.
Building Blocks of Nucleic Acids →Insertion of a LINE-1 element into exon 14 of the factor VIII gene is a documented cause of severe hemophilia A in multiple unrelated families, demonstrating that active transposition can disrupt a medically critical gene. The inserted element spans roughly 3.8 kilobases and completely abolishes normal factor VIII production.
Linkage
/ LINK-ij / · English: link + -age
Linkage is the tendency of genes located close together on the same chromosome to be inherited together rather than independently, because crossing over between them is rare.
Genes on different chromosomes or far apart on the same chromosome assort independently according to Mendel’s law of independent assortment, but closely linked genes violate this expectation. The strength of linkage is inversely proportional to the physical distance between loci, quantified in centimorgans, where one centimorgan corresponds to a one percent recombination frequency. Linkage mapping using recombination frequencies was the first method for establishing the linear order of genes on chromosomes, pioneered by Alfred Sturtevant in 1913 using Drosophila melanogaster.
Thomas Hunt Morgan's discovery of genetic linkage in Drosophila in 1910 provided the first experimental evidence that genes are physically located on chromosomes, directly supporting the chromosome theory of heredity.
Linkage is not the same as linkage disequilibrium. Linkage describes the physical proximity of genes on a chromosome, while linkage disequilibrium describes the non-random association of specific alleles at different loci within a population.
The genes encoding red-green color vision pigments and the factor VIII clotting protein both reside on the human X chromosome and show strong genetic linkage, so they tend to be co-inherited within families. Recombination between these loci occurs in fewer than 5 percent of meioses, reflecting their relatively close chromosomal positions.
Linked Genes
/ LINKT jeenz / · English: linked + genes
Linked Genes are genes located on the same chromosome that tend to be inherited together because their physical proximity reduces the probability of recombination separating them during meiosis.
All genes on the same chromosome belong to the same linkage group, and the number of linkage groups in a species equals its haploid chromosome number. Linked genes that are very close together show little recombination and are transmitted as a unit in nearly all gametes. Detection of linked genes through deviations from independent assortment ratios was one of the earliest approaches to constructing genetic maps, first applied systematically to Drosophila melanogaster by Thomas Hunt Morgan’s laboratory in the early 1900s.
The human X chromosome carries more than 800 protein-coding genes in a single linkage group, which is why multiple distinct conditions including hemophilia A, red-green color blindness, and Duchenne muscular dystrophy all show X-linked inheritance patterns.
Linked genes are not always inherited together. Crossing over during meiosis can separate linked genes, with separation frequency increasing as the distance between them grows.
What Is a Homologous Chromosome? →In the fruit fly (Drosophila melanogaster), the genes for body color and wing venation pattern reside on chromosome 2 and are strongly linked, producing recombinant offspring at frequencies well below the 50 percent expected from independent assortment. When the two loci are separated by roughly 17 centimorgans, recombinant classes appear in only about 17 percent of progeny rather than 50 percent.
Locus
/ LOH-kus / · Latin: locus (place)
Locus is the specific physical location of a gene or other DNA sequence on a chromosome, defined by its position relative to flanking markers.
Each gene occupies a characteristic locus that is consistent across individuals of the same species, allowing alleles at the same locus to be compared between individuals. Quantitative trait loci, abbreviated QTL, are chromosomal regions statistically associated with variation in continuous traits such as height or blood pressure, identified through mapping crosses or genome-wide association studies. The plural of locus is loci, and a diploid organism carries two alleles at each autosomal locus, one on each homologous chromosome.
Cytogenetic notation specifies a locus by chromosome number, arm designation, and band position, as in 7q31 for the cystic fibrosis gene.
Fine-mapping of disease loci using dense SNP arrays has reduced the search interval for some Mendelian disease genes to fewer than 100 kilobases, cutting the candidate gene list from hundreds to just a handful.
A locus is not the same as an allele. The locus is the fixed position on the chromosome, while the allele is the specific DNA sequence variant present at that position in a given individual.
The cystic fibrosis locus at chromosome 7q31.2 has been precisely mapped, so molecular diagnostic labs can target that exact region when screening for CFTR mutations across more than 2,000 known disease-causing variants. Knowing the locus coordinates the search to a defined chromosomal address rather than scanning the entire genome.