Atypical Inheritance

Bio 1 SDJacinto Institute of Biology UP Diliman

Incomplete Dominance
Snapdragons - when homozygous red (RR) snapdragons are crossed with homozygous white (rr) plants, the F1 generation has the genotype Rr and is pink. When these F1 plants are crossed, one gets a ratio of 1 red (RR), 2 pink (Rr) and one white (rr). Here the heterozygous phenotype is intermediate between the two parents. Carnations the same


Roan cow

Both alleles are expressed but there is no blending

Polygenic traits
Determined by more than 1 gene Human polygenic traits include 1. Height 2. SLE (Lupus) 3. Weight 4. Eye Color 5. Intelligence 6. Skin Color 7. Many forms of behavior BioBookgeninteract.html


effect of one gene on more than one characteristic. Examples A. "frizzle-trait" gene in chickens Primary result - production of defective feathers Secondary results -include increased adaptation to warm temperatures, increased metabolic rate, decreased egg-laying, changes in heart, kidney and spleen

- B. white cats with blue eyes are often deaf, white cats with a blue and an yellow-orange eye - deaf on the side with the blue eye 150/gene/mol_gen.htm

Genetic basis of some diseases

Autosomal recessive inheritance
An abnormal gene on one of the autosomal chromosomes (one of the first 22 "non-sex" chromosomes) from each parent is required to cause the disease. People with only one abnormal gene allele are called carriers, but since the gene is recessive they do not exhibit the disease. In other words, the normal gene of the pair can supply the function of the gene so that the abnormal gene is described as acting in a recessive manner. BOTH parents must be carriers in order for a child to have symptoms of the disease; a child who inherits the gene from one parent will be a carrier.

About one in 10,000 children - born with phenylketoneuria (PKU). Caused by missing enzyme that breaks down phenylalanine, one of the building blocks of protein found in a normal diet. the

Serious if left untreated, causing mental impairment. However, PKU is treated successfully by controlling levels of phenylalanine in the diet. All babies in the UK-heel-prick test shortly after birth. If PKU is diagnosed babies are given a special diet. Autosomal recessive inheritance ency/imagepages/2962.htm

Tay-Sachs disease
Rare and extremely severe genetic condition affecting the brain and nerves.

A baby with Tay-Sachs disease appears normal at birth, but development starts to slow down at about 6 months of age. Gradually, the child becomes blind, deaf and paralyzed Children with Tay-Sachs disease usually die before the age of five. There is no cure for this devastating disorder, and no effective treatment. Autosomal recessive mode of inheritance

Other Autosomal Recessive (AR) diseases:
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Sugar intolerance: galactose, fructose, saccharose, lactose. Most amino acid disorders : tyrosinosis, cystinosis, leucinosis. albinism variants (except ocular albinism which is RLX) etc… Several lipid metabolism diseases. Several disorders of hormone synthesis, mainly thyroid and adrenal. Cystic fibrosis ( 1 in 22 of whites in UK are carriers of
CF- chrosomosome 7)

Autosomal Dominance Defined

A single, abnormal gene on one of the autosomal chromosomes from either parent can cause certain diseases. One of the parents will usually have the disease (since it is dominant) in this mode of inheritance. Only one parent must have an abnormal gene in order for the child to inherit the disease.

Other Autosomal Dominant Diseases/Conditions :
•Achondroplasia •Aniridia •Polydactyly •Adenomatous polyposis of the colon

Marfan's syndrome
(disorder of the connective tissue )
mutation of the fibrillin gene-produces mutant fibrillin which weakens tendons, connective tissues and ligament; every person in affected family has unique mutation in fibrillin causes skeletal defects typically recognized in a tall, lanky person, exhibit long limbs and spider-like fingers chest abnormalities, curvature of the spine particular set of facial features including a highly arched palate and crowded teeth. cardiovascular abnormalities - most significant of the defects (may include enlargement of base of aorta). Autosomal dominant mode of inheritance ency/imagepages/9611.htm marfans-syndrome.html

Huntington's Disease (Huntington’s chorea)
Repeated trinucleotide CGG in chrom 4 mutated to CAG -adds a string of glutamines (Gln) to the encoded huntingtin protein; the abnormal protein interferes with synaptic transmission in parts of the brain and leads to death of these brain cells. Symptoms: (observed with gradual progression of disease)
•depression •difficulty in speaking and swallowing •occasional delusions, hallucinations •cognitive decline •rapid, jerky involuntary movements (chorea) •obsessive compulsive disorders. Autosomal dominant mode of inheritance

Family of 5 children whose mom (deceased, inset) had HD

Fragile X syndrome
(discovered in 1991) Caused by full mutation of FMR1 gene Other individuals are carriers- they have a small defect in FMR1 ("premutation") but do not show symptoms. Carrier men (transmitting males) pass the premutation to all their daughters but none of their sons. Each child of a carrier woman has a 50% chance of inheriting the gene. The Fragile X premutation can be passed silently down through generations in a family before a child is affected by the syndrome.

A premutation is susceptible to expansion after passage through a female meiosis. The larger the size of a premutation, the more the risk of expansion to a full mutation in the offspring. Male and female with premutation are not affected but their offspring will be.

Common Symptoms/Manifestations of Fragile X
-attention deficit and hyperactivity -anxiety and unstable mood -autistic-like behaviors -long face, large ears, flat feet -hyperextensible joints, especially fingers -Seizures (epilepsy) affect about 25% of people with fragile X  mental impairment, ranging from learning disabilities to mental retardation Boys - more severely affected than girls; most have mental retardation

Girls-only 1/3 to 1/2 have significant intellectual impairment; the rest have either normal IQ or learning disabilities.

Emotional and behavioral problems - common in both sexes; Most boys and some girls have some symptoms of autism, but many are very social and interested in other people.

Pattern of inheritance of the fragile X syndrome in one family. The number of times that the trinucleotide CGG is repeated is given under the symbols. The gene is on the X chromosome, so women (circles) have two copies of it; men (squares) have only one. People with a gene containing 80–90 repeats are normal (light red), but this gene is unstable, and the number of repeats can increase into the hundreds in their offspring. Males who inherit such an enlarged gene suffer from the syndrome (solid red squares). (Data from C. T. Caskey, et al.). BiologyPages/M/Mutations.html FragileX_cover.htm

X-linked diseases
1. Phenotypic expression more common in males 2. Sons cannot inherit the trait from their fathers, but daughters can. Sons inherit their Y chromosome from their father.

Examples of X linked diseases/condition :

-Colour blindness -Hemophilia A and B -Duchenne muscular dystrophy -Incontinentia pigmentosum -G6PD deficiency

Other genetic diseases
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Familial (Familial Adenomatous Polyposis) Multifactorial diseases (genetics and environment have roles to play e.g. cardiovascular, stroke, obesity )

Genetic testing and counseling
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Some diseases tended to run in families Eugenics- study of how to improve human qualities through directed breeding practices, Eugenicists felt that traits like intelligence, criminal behavior and artistic ability could be traced to simple dominant or recessive genes. By encouraging people with "good" traits to have more children and encouraging people with "bad" traits to have fewer or no children, eugenicists felt they could rid the world of many social problems.

Although many rejected eugenics because of Nazi horror, many still believed in it. Hence, the first medical genetics clinics opened in the United States in the mid1940's and early 1950's Medical geneticists conducted "hereditary counseling clinics" with families, examined affected individuals and drew pedigrees to help clarify the genetic component of diseases and birth defects. They worked primarily with relatively common diseases and conditions such as sickle cell anemia, achondroplasia. Only little genetic information at that time.

The practice of genetic counseling took a giant leap forward in 1967 with the first amniocentesis. Amniocentesis, while tremendously informative, is not a fool-proof process. It carries risks including potential infection and/or miscarriage. Also there are limitations on what amniocentesis can predict about the baby. cat.asp?cat=972 dana/250/25003_10.html

Pedigree –
determines a person's risk of developing a genetic disease •helps make a diagnosis of a genetic disease, •determines the risk of having a child with a genetic disease Pedigree includes relatives up to 3rd degree - includes vital medical information-birth date, age at death, cause of death, health problems, results of genetic tests.

Pedigree on alkaptonuria

Medical tests could be specialized like a (chromosome study) or DNA analysis (detect gene mutations) or more general- X-ray, ultrasound, urine analysis, skin biopsy, physical exam.

After medical tests genetic counselor may be able to make a diagnosis, or determine a person’s risk for a genetic disease. Biggest challenge - help families cope with the emotional, psychological, medical, social and economic consequences of genetic disease.

Newborn screening for genetic disorders units/disorders/newborn/ ehsphl/phl/newborn/

Newborn screening for genetic disorders was started in the US by Dr.Robert Guthrie for phenylketonuria. There is now 100% implementation in the USA. In Asia- Japan, Singapore, Hong kong, Taiwan and Thailand also have 100% coverage. Introduced in the Philippines in 1996 by the Newborn Screening Study group. This includes now PKU, congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), galactosemia and recently glucose 6 phosphate dehydrogenase (G6PD) deficiency Local statistics state that at least 33,000 newborns are saved annually from mental retardation and death due to the screening

Newborn Screening Act of 2004 in the Philippines R.A. 9288
Requires that every baby born in the Philippines will be offered a chance for newborn screening for the 5 disorders which may potentially prevent mental retardation and death. Approved April 7, 2004 Despite govt and private efforts, only 3% of newborn are screened. Lack of health professional and public awareness of benefits of newborn screening.  Screening for 5 disorders-net annual benefit of $12 M

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