STUDIES OF HUMAN FAMILIES FOR GENETIC LINKAGE

One of the most important and exciting activities in human
genetics involves the elucidation of man's genetic map by linking
gene loci to each other and to specific chromosomes. Knowledge of
man's genetic map will form the basis for antenatal and early post-
natal detection of many hereditary disorders, will permit us to
understand the molecular pathogenesis of the abnormalities resulting
from various chromosomal abnormalities and, looking to the future,
is fundamental for any attempts at genetic engineering. Linkage
information in man 1s obtained primarily by two types of investigation,
one involving in vitro interspecific somatic cell hybridization, and
the other involving analysis of segregation of various qenetic markers
and marker chromosomes in human families. The latter approach,
family studies for linkage determinations, has been an important
and ongoing activity in the Genetics Laboratory of the Department
of Pediatrics at Stanford University School of Medicine. This
laboratory has the capability, facilities and experience in testing
for a number of human polymorphic gene markers (mostly of blood)
including red blood cell antigens, serum proteins and erythrocyte
enzymes, and a number of families with disorders determined by x-linked
or autosomal dominant genes have been studied for co-segregation of
these genes and the various polymorphic marker genes. More recently
we have been able, through close collaboration with the Tissue Typing

Laboratory (Dr. Rose Payne) at Stanford, to incorporate the highly
-2-

polymorphic HL~A system into our family studies, improving the power
for detecting linkage. Presently, we are applying techniques for
giemsa and fluorochrome banding of human chromosomes to our linkage
studies, taking advantage of these highly informative methods to
identify specific chromosomes (or portions thereof) and to detect
differences between homologous chromosomes within families in order
to follow co-segregation of chromosomes and gene markers. Thus, we
have expanded our capabilities for detecting linkage between gene loci
and between loci and chromosomes, and we willsstudy, in a systematic
manner, human families showing evidence of segregation of dominant
and x-linked traits or cytogenetic markers. These linkage studies
form one of the prdjects of a recently developed collaborative effort
of the Departments of Pediatrics and Genetics at Stanford in human
genetics research. We are committed to an ongoing program in genetic
linkage studies in man, and we are seeking support for thts important

activity.